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Sample Dossier

Sample Dossier

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XYZ PHARMACEUTICAL

PRODUCT REGISTRATION DOSSIER

PARACETAMOL TABLET 500 MG

A Product of Neutral Code Marketed/ Imported by

: : : :

Date of submission

1 Contact :: info@icpc.biz Website :: http://icpc.biz/PharmaceuticalDossier.aspx

XYZ PHARMACEUTICAL

SCHEDULE

APPLICATION FOR REGISTRATION OF A DRUG CONFIDENTIAL

DEMOCRETIC REPUBLIC OF--------MINISTRY OF PUBLIC HEALTH DIRECTION OF PHARMACY, DRUG & LABORATORY TECHNICAL DIVISION SECRETARIAT-GENERAL

PART-I 1. NAME OF APPLICANT BUSINESS ADDRESS : :

TELEPHONE NUMBER FAX 2. NAME OF PRODUCT TO BE REGISTERED TYPE OF FORMULATION TO REGISTERED PRESENTATION OF THE PRODUCT

: :

:

:

:

2 Contact :: info@icpc.biz Website :: http://icpc.biz/PharmaceuticalDossier.aspx

XYZ PHARMACEUTICAL
3. IDENTIFICATION(PHYSICAL APPERANCE OF THE PRODUCT 4. THERAPEUTIC CLASSIFICATION 5(a) NAME OF BUSINESS ADDRESS OF MANUFACTURER (b) COUNTRY OF ORIGIN :

: :

(6) NAME OF LOCAL DISTRIBUTOR BUSINESS ADDRESS OF LOCAL DISTRIBUTOR

:

:

TELEPHONE NUMBER FAX NUMBER (7) NAME AND SIGNATURE OF THE AUTHORIZE PERSON DATE SIGNATURE OFFICIAL STAMP

: :

: : : :

3 Contact :: info@icpc.biz Website :: http://icpc.biz/PharmaceuticalDossier.aspx

biz Website :: http://icpc.biz/PharmaceuticalDossier.XYZ PHARMACEUTICAL PART I SUMMARY OF THE DOSSIER 4 Contact :: info@icpc.aspx .

aspx .biz/PharmaceuticalDossier.XYZ PHARMACEUTICAL CTD Module I ADMINISTRATIVE DATA (1) SITE MASTER PLAN OF PLANT (2) COMPANY PROFILE IN SHORT (3) ATTESTED COPY OF MANUFACTURING LICENCE (4) ATTESTED COPY OF PRODUCT PERMISSION FROM FDCA (5) ATTESTED COPY OF COPP (6) ATTESTED COPY OF WHO/GMP CERTIFICATE (7) COA OF SAMPLE (8) ATTESTED COPY OF WHOLE SELL LICENCE. (9) LETTER OF AUTHORISATION 5 Contact :: info@icpc.biz Website :: http://icpc.

___________________________________________________________________ PRODUCT OWNER’S NAME AND ADDRESS HEREBY APPOINT __________________________________________________________ APPLICANT’S NAME AND ADDRESS TO APPLY FOR REGISTRATION OF OUR PHARMACEUTICAL PRODUCT PRODUCT NAME.XYZ PHARMACEUTICAL MODEL OF LETTER OF AUTHORISATION COMPANY’S LETTERHEAD LETTER OF AUTHORISATION WE.biz/PharmaceuticalDossier.aspx . THEY WILL BE THE MARKETING AUTHORISATION HOLDER OF THE REGISTRATION CERTIFICATE AND BE RESPONSIBLE FOR ALL MATTERS PERTAINING TO THE REGULATION OF THIS PRODUCT. SIGNATURE : __________________ Date : 6 Contact :: info@icpc.biz Website :: http://icpc. DOSAGE FORM AND STRENGTH WITH THE DRUG REGULATORY AUTHORITY IN (STATE COUNTRY) ON OUR BEHALF .

biz Website :: http://icpc.: OWNER OF DRUG DATE OF ISSUE: DATE OF EXPIRY: SALES CATEGORY: VARIATION: MANUFACTURER 7 Contact :: info@icpc.: ASSESSMENT FEES: REGISTRATION CERTIFICATE NO. APPLICANT DATE OF APPLICATION: APPLICATION NO.XYZ PHARMACEUTICAL Department of Health Food and Drug Administration Summary Drug Information NAME ADDRESS PHONE/FAX FOR OFFICIAL USE.biz/PharmaceuticalDossier.aspx .

Paracetamol is one of the most common analgesics used in children.1X500T. DOSAGE : Adults: One to two tablets every 4 to 6 hours up to a maximum of 8 tablets daily. PACK SIZE) INDICATION: Relief mild to moderate pain and fever. The recommended dose for children is 15mg/kg orally every four hours. 8 Contact :: info@icpc.XYZ PHARMACEUTICAL BRAND NAME COMPOSITION (INCLUDING EXCIPIENTS & COLORING SUBSTANCE) NON PROPRIETARY NAME DOSAGE FORM STRENGTH THERAPEUTIC CATEGORY PARACETAMOL BP TABLET 500MG ANALGESIC AND ANTIPYRATIC 1X100T.biz/PharmaceuticalDossier. It can also be used rectally in children with a dose of 0mg/kg.aspx .50 The maximum daily dose should be limited to 90mg/kg up to a total of 4000mg. Children 6-12 years: One tablet 3 to 4 times daily as required.10X10T PARACETAMOL BP 500MG PRESENTATION(TYPE OF PACKING.biz Website :: http://icpc.

aspx .XYZ PHARMACEUTICAL PROFORMA STATEMENT: S. 10X10T : 3Years from the date of manufacturing : US$ : 9 Contact :: info@icpc.NO.biz/PharmaceuticalDossier.biz Website :: http://icpc. TRADE NAME GENERIC NAME OR FORMULA EACH TABLET CONTAINS: 1 PARACETAMOL BP 500MG ANALGESIC & ANTIPYRETIC INDICATIONS REMARK PACKING LIFE FOB PRICE MANUFACTURER : 1x100T.

S.biz/PharmaceuticalDossier.1 NAME OF THE ACTIVE SUBSTANCE(S) PARACETAMOL BP 500 MG 1 A 1. 1 A 2.S.aspx .biz Website :: http://icpc.2 PHARMACOTHERAPEUTIC CLASSIFICATION ANALGESIC & ANTIPYRATICS 1A2 PHARMACEUTICAL FORM AND STRENGTH PHARMACEUTIACLS DOSAGE : ORAL TABLET PARACETAMOL TABLET 500 MG EACH UN COATED TABLET CONTAINS: PARACETAMOL BP ---------500 MG EXCIPIENTS-------------------Q.3 Storage STORE IN COOL DRY PLACE 10 Contact :: info@icpc.1 Route of administration ORAL 1 A 2.XYZ PHARMACEUTICAL IA 1A1 ADMINISTRATIVE DATA PROPOSED TRADE NAME OF THE PHARMACEUTICAL PRODUCT PARACETAMOL TABLET BP 500 MG EACH UNCOATED TABLET CONTAINS: PARACETAMOL BP ---------500 MG EXCIPIENTS---------------------Q. 1 A 1.2 Container EACH BOX OF 10 X 10TABLETS 200 BOXES IN EACH CORRUGATED BOX Shelf-life 36 MONTHS 1 A 2.

00 MG 11 Contact :: info@icpc.00 50.biz Website :: http://icpc.00 Unity mg Reference BP : .00 mg mg mg mg mg mg mg BP BP BP BP BP USP BP Quantity 500.00 5. 620.aspx ..XYZ PHARMACEUTICAL IA4 QUALITATIVE AND QUANTITATIVE COMPOSITION EACH TABLETS CONTAINS Nº I 1.00 27.00 4. II 1 2 3 4 5 6 7 Name ACTIVE SUBSTANCE(S) PARACETAMOL EXCIPIENT(S) LACTOSE MICRO CRYSTALINE CELLULOSE STARCH MAGNESIUM STEARATE SODIUM STARCH GLYCOLATE COLLOIDAL SILICON DIOXIDE PURIFIED TALC 23..00 5.biz/PharmaceuticalDossier.00 6.

biz Website :: http://icpc.biz/PharmaceuticalDossier.aspx .XYZ PHARMACEUTICAL CTD Module II & III SUMMARY OF PRODUCT CHARACTERISTICS (SPC) 12 Contact :: info@icpc.

aspx .XYZ PHARMACEUTICAL II B II B 1 SUMMARY OF PRODUCT CHARACTERISTICS (SPC) SUMMARY OF PRODUCT CHARACTERISTICS (SPC) II B 1.1 Proposed trade name of the pharmaceutical product PARACETAMOL TABLET BP 500 MG II B 1.biz Website :: http://icpc.biz/PharmaceuticalDossier.2 Qualitative and quantitative composition 13 Contact :: info@icpc.

00 5. II 1 2 3 4 5 6 7 Name ACTIVE SUBSTANCE(S) PARACETAMOL EXCIPIENT(S) LACTOSE MICRO CRYSTALINE CELLULOSE STARCH MAGNESIUM STEARATE SODIUM STARCH GLYCOLATE COLLOIDAL SILICON DIOXIDE PURIFIED TALC 23.00 mg mg mg mg mg mg mg MG BP BP BP BP BP USP BP Quantity 500.00 6.00 50.biz Website :: http://icpc.00 27.00 620.biz/PharmaceuticalDossier.00 5 .XYZ PHARMACEUTICAL EACH TABLETS CONTAINS Nº I 1.00 4.aspx .00 Unity mg Reference BP 14 Contact :: info@icpc.

biz/PharmaceuticalDossier.biz Website :: http://icpc.aspx .XYZ PHARMACEUTICAL RAW MATERIAL SPECIFICATIONS 15 Contact :: info@icpc.

6. 7.0% 3. freely soluble in alcohol.XYZ PHARMACEUTICAL SUBJECT: DEPARTMENT: MATERIAL NAME: PARACETAMOL BP RAW MATERIAL SPECIFICATION QUALITY CONTROL SPEC NO: RMS/PARA/2004 EFFECTIVE DATE: REVIEW DATE: Two Years SR NO 1. 9. 4.aspx .biz Website :: http://icpc.1% 99. Complies the test Complies the test Complies the test Complies the test NMT 0. very slightly soluble in ether and in methylene chloride. TEST CHARACTERS SOLUBILITY SPECIFICATION A white. 8. crystalline powder. sparingly soluble in water.biz/PharmaceuticalDossier.0-101. IDENTIFICATION RELATED SUBSTANCE 4-AMINOPHENOL HEAVY METALS LOSS ON DRYING SULPHATED ASH ASSAY 16 Contact :: info@icpc. 5.5% NMT 0. 2.

5. 3. 6.biz/PharmaceuticalDossier. 9. 2.biz Website :: http://icpc.0 To comply the test To comply the test To comply the test To comply the test To comply the test To comply the test To comply the test NMT 0.XYZ PHARMACEUTICAL SUBJECT DEPARTMENT : : RAW MATERIAL SPECIFICATION QUALITY CONTROL MATERIAL NAME : PURIFIED WATER SPEC NO: RMS/PW/2004 EFFECTIVE DATE REVIEW DATE : : Two Years SR NO 1. 8. 10. 4. TEST CHARACTERS pH Oxidisable substance Chloride Nitrate Sulphate Ammonium Calcium & Magnesium Heavy metal Residue on evaporation Microbial contamination SPECIFICATION A clear liquid.0-7. colorless and tasteless 5.0001% To comply the test 17 Contact :: info@icpc.aspx . 7. 11.

1.1M NaOH is required. NMT 0. 6. Appearances of solutionq Acdidty or alkalinity Specific optical rotation Absorbance (at 270 to 300 nm) Heavy metals (limit test) Water Sulphated ash Microbial limit test Additional test : 1. : Lactose BP SPECIFICATION White. 10. I. 9. 3. crystalline powder Freely but slowly soluble in water TEST PARAMETERS Description Solubility Identification A.biz Website :: http://icpc.07. no. Storage: Black particles Free from black particles. absorption spectrum B. 2.5% NMT 0. +54. Store in well closed containers 18 Contact :: info@icpc. 5. NMT 1 ppm 4. To comply Solution is clear and colourless. 11.9° Not greater than 0.R.4ml of 0.XYZ PHARMACEUTICAL XYZ PHARMACEUTICAL QUALITY ASSURANCE DPEARTMENT RAW MATERIAL SPECIFICATION Name of Material Sr. 4.4° to +55. By TLC C: Colour test D: Test for water To comply To comply Red colour develops. 8.biz/PharmaceuticalDossier.1% Complies with the test for Escherichia coli.aspx .5% to 5. 7.

fine or granular powder.P.5 for the supernatant liquid. Complies as per B. Practically insoluble in water.P. Complies as per B.P. 19 Contact :: info@icpc.biz/PharmaceuticalDossier. 5. Maximum 7.aspx .biz Website :: http://icpc. in dilute acids and in a 50 g/1 solution of sodium hydroxide. in toluene.0 % Maximum 0. in acetone. Maximum 0.XYZ PHARMACEUTICAL Test Specifications of Microcrystalline Celiulosel02fMCCP) B.1 % Description Solubility Identification pH Conductivity Ethersoluble substances Water-soluble substances Heavy metals Loss on drying Sulphated ash Microbial contamination Complies as per B. Specifications White or almost white.P.05 % Maximum 0. in ethanol.0 to 7.25 % Maximum 10 ppm.

XYZ PHARMACEUTICAL Specifications of Maize Starch B. determined by plate count. white to slightly yellowish.6 % Total viable aerobic count NMT 103 bacteria and 102 fungi per gram. Practically insoluble in cold water and in ethanol (96 per cent). 4. Maximum 10 ppm. Test Description Specifications Matt. which creaks when pressed between the fingers. Solubility Identification pH Foreign matter Oxidizing substances Sulphur dioxide Iron Loss on drying Sulphated ash Microbial contamination 20 Contact :: info@icpc.aspx Website :: . Maximum 20 ppm.0% Maximum 0.biz http://icpc.P.biz/PharmaceuticalDossier.0.0 to 7. Complies as per B. Maximum 15.P.P. very fine Powder. It complies with the test for Escherichia coli. The presence of granules with cracks or irregularities on the edge is exceptional. Maximum 50 ppm. Complies as per B.

01 02 03 04 05 06 07 08 09 10 11 12 13 Characters Identification Appearance of solution Acidity or Alkalinity Chloride Sulphates Cadmium Lead Nickel Loss on drying Magnesium Fatty acid composition Microbial Contamination 14 15 Assay Fatty acid composition 21 Contact :: info@icpc. 1 Year 1 year after expiry of the material Limit Should Comply as per BP (C).0 % 4.1 % NMT 0.biz/PharmaceuticalDossier.5 % NMT 3 ppm of Cd NMT 10 ppm of Pb NMT 5 ppm of Ni NMT 6.0% NLT 40% of stearic acid Sum of stearic acid & palmitic acid NLT 90% Total viable aerobic count not more than 103 micro-organisms per gram. determined by plate count.XYZ PHARMACEUTICAL XYZ PHARMACEUTICAL QUALITY ASSURANCE DPEARTMENT RAW MATERIAL SPECIFICATION Name of Material: Magnesium Stearate BP Lubricant In-active material BP ’ 10 GMS.biz Website :: http://icpc.0 – 5. From each container 20 GMS. Should comply as per BP ‘ Should Comply as per BP Should Comply as per BP NMT 0. (D).aspx . It complies with the test for Escherichia coli) Should Comply as per BP SHOULD COMPLY AS PER BP (A) General Information: Category Status Tested as per Sample Size Qnty for controlled sample Time for Re-testing Retention time for controlled sample (B) Testing Parameters: Test Sr.

0 % It complies with the test for Escherichia coli and Salmonella Lubricant In-active material BP 10 GMS.biz Website :: http://icpc. From each container 20 GMS.(D) -should comply as per BP Should comply as per BP 5.5 Should comply as per BP NMT 1.(B).(C).5 – 7. 01 02 03 04 05 06 07 08 09 10 IDENTIFICATION Appearance of gel PH Sodium Glycollate Sodium Chloride Heavy Metals Iron Loss on Drying Microbial Contamination Test Characters Limit Should comply as per BP (A).biz/PharmaceuticalDossier.aspx . 1 Year 1 year after expiry of the material 22 Contact :: info@icpc.0 % NMT 20 ppm NMT 20 ppm NMT 7.XYZ PHARMACEUTICAL XYZ PHARMACEUTICAL QUALITY ASSURANCE DPEARTMENT RAW MATERIAL SPECIFICATION Name of Material: Sodium Starch Glycollate BP (A) General Information: Category Status Tested as per Sample Size Qnty for controlled sample Time for Re-testing Retention time for controlled sample (B) Testing Parameters: Sr.

12.5% NMT 10 ppm NMT 7. 7. 4.25% 17.0% NMT 0. 11.aspx . Description Solubility Identifications A: I.0% to 19. Additional test : 1. pH Water-insoluble substances Aluminium (on atomic absorption spectrometry) Calcium (on atomic absorption spectrometry) Iron (on atomic absorption spectrometry) Magnesium (on atomic absorption spectrometry) Lead (on atomic absorption spectrometry) Loss on ignition (at 1050°c to 1100°c) Microbial contamination To comply White.biz/PharmaceuticalDossier. spectrophotometry B: Precipitate reaction C: Reaction of Silicates.0% w/w Total visible aerobic count is not more than 102 aerobic bacteria and fungi per gram. crystalline precipitate is formed. 6.XYZ PHARMACEUTICAL XYZ PHARMACEUTICAL QUALITY ASSURANCE DPEARTMENT RAW MATERIAL SPECIFICATION Name of Material: Purified Sr. 1. 3. 2. Talc SPECIFICATION White coloured fine powder Practically insoluble in water and in dilute solutions of acids and alkali hydroxides. Black particles Free from black particles 23 Contact :: info@icpc.2% NMT 2. 10. TEST PARAMETERS no. 8. 5.0 to 9.9% NMT 0.biz Website :: http://icpc.0 NMT 0. To comply 7. 9.R.

5 Solubility Identification pH (in a 1 in 25 dispersion) Loss on drying Loss on ignition Arsenic Organic volatile impurities Assay NMT 2.5% w/w NMT 2% w/w The limit is 8 ug per g Meets the requirements NLT 99% and NMT 100.biz http://icpc.biz/PharmaceuticalDossier. white.5% of Si02 24 Contact :: info@icpc.XYZ PHARMACEUTICAL Specifications of Silicon Dioxide U.S.P. 3.P Test Description Specifications Light. Insoluble in water and in acid (except hydro fluoride).5 to 5.S. soluble in hot solutions of alkali hydroxides To comply as per U. nongritty powder of extremely fine particle size (about 15 nm).aspx Website :: .

D.biz Website :: http://icpc. comparing with the spectrum obtained with lactose CRS. C.XYZ PHARMACEUTICAL Name of Material Tested as per LACTOSE BP BRITISH PHARMACOPEIA C12H22O11. freely but slowly soluble in water.3 10039-26-6 Ph Eur Definition Lactose monohydrate is the monohydrate of O-b-D-galactopyranosyl-(1®4)-a-Dglucopyranose. 25 Contact :: info@icpc. Examine by infrared absorption spectrophotometry (2. It may be modified as to its physical characteristics and may contain varying proportions of amorphous lactose. D. practically insoluble in alcohol. Second identification B.biz/PharmaceuticalDossier. A. crystalline powder.H2O 360.aspx .24). Characters A white or almost white. Identification First identification A.2.

25 g in 5 ml of water R. Method II). Examine by thin-layer chromatography (2. measured accurately since a slight excess of water produces cloudiness. Repeat the development immediately.2. Test solution Dissolve 10 mg of the substance to be examined in a mixture of 2 volumes of water R and 3 volumes of methanol R and dilute to 20 ml with the same mixture of solvents. glucose CRS. Add 5 ml of ammonia R and heat in a water-bath at 80°C for 10 min. Dry the plate in a current of warm air.1M sodium hydroxide is required to change the colour of the indicator to pink.2. heating to 50°C.2.27).2. Heat at 130°C for 10 min.3 ml of phenolphthalein solution R. 25 volumes of anhydrous acetic acid R and 50 volumes of ethylene chloride R. Apply separately to the plate 2 ml of each solution and thoroughly dry the starting points. Specific optical rotation (2.XYZ PHARMACEUTICAL B. Acidity or alkalinity Dissolve 6. Reference solution (b) Dissolve 10 mg each of fructose CRS. The solution is colourless. It complies with the test for water (see Tests). Tests Appearance of solution Dissolve 1. Not more than 0. using silica gel G R as the coating substance.7) 26 Contact :: info@icpc. A red colour develops.4 ml of 0. Dissolve 0. The principal spot in the chromatogram obtained with the test solution is similar in position.biz/PharmaceuticalDossier. Dry the plate in a current of warm air and spray evenly with a solution of 0. D.0 g in water R. Reference solution (a) Dissolve 10 mg of lactose CRS in a mixture of 2 volumes of water R and 3 volumes of methanol R and dilute to 20 ml with the same mixture of solvents. colour and size to the principal spot in the chromatogram obtained with reference solution (a). lactose CRS and sucrose CRS in a mixture of 2 volumes of water R and 3 volumes of methanol R and dilute to 20 ml with the same mixture of solvents.0 g by boiling in 25 ml of carbon dioxide-free water R.5 g of thymol R in a mixture of 5 ml of sulphuric acid R and 95 ml of alcohol R. Develop over a path of 15 cm using a mixture of 10 volumes of water R. C.2. The test is not valid unless the chromatogram obtained with reference solution (b) shows four clearly separated spots. cool and add 0.biz Website :: http://icpc. dilute to 10 ml with the same solvent and allow to cool.1) and not more intensely coloured than reference solution BY7 (2. after renewing the mobile phase.aspx . The solution is clear (2. 15 volumes of methanol R.

biz Website :: http://icpc.1 per cent. Water (2. It complies with the test for Escherichia coli (2.XYZ PHARMACEUTICAL Dissolve 10. Sulphated ash Not more than 0. To 1. Dilute 1.6. At wavelengths from 270 nm to 300 nm. At wavelengths from 210 nm to 220 nm.25. calculated with reference to the anhydrous substance.aspx .1M hydrochloric acid and dilute to 20 ml with water R. determined on 0.0 ml with water R.5 per cent. Microbial contamination Total viable aerobic count (2.0 g in water R with warming.2.12) not more than 102 micro-organisms per gram. the absorbance is not greater than 0. 27 Contact :: info@icpc.13). Absorbance (2.4.2 ml of dilute ammonia R1.07. Examine the solution from 210 nm to 300 nm. Allow to cool and add 0.0 ml with water R.6. evaporate to dryness on a water-bath and ignite to constant mass. heating to 50°C.12) 4.0 ml with the same solvent (solution A).0 g add 1 ml of sulphuric acid R. Heavy metals (2. 12 ml of the solution complies with limit test A for heavy metals (5 ppm).5 per cent to 5. determined by plate-count. Storage Store in an airtight container . add 1 ml of 0. using a mixture of 1 volume of formamide R and 2 volumes of methanol R as the solvent. the absorbance is not greater than 0.5.0 g in 80 ml of water R.4° to +55.0 g in boiling water R and dilute to 10.04. The absorbance of the solution measured at 400 nm is not greater than 0. The specific optical rotation is +54.9°. Allow to stand for 30 min and dilute to 100.8) Dissolve 4.50 g by the semi-micro determination of water.biz/PharmaceuticalDossier.0 ml of solution A to 10.25) Dissolve 1. Prepare the standard using lead standard solution (1 ppm Pb) R.

Immediately purge the solution with nitrogen R. Place about 10 mg on a watch-glass and disperse in 2 ml of iodinated zinc chloride solution R.blue. Determine the intrinsic viscosity. partly depolymerised cellulose prepared by treating alpha-cellulose.biz/PharmaceuticalDossier.XYZ PHARMACEUTICAL Name of Material Tested as per MICROCRYSTALLINE CELLULOSE BP BRITISH PHARMACOPEIA Action and use Pharmaceutical aid. Transfer 7. practically insoluble in water. using the Intrinsic Viscosity Table (Table 315-1 see Cellulose. The substance becomes violet. in toluene and in dilute acids and in a 50 g/l solution of sodium hydroxide. Transfer 1. using a suitable capillary viscometer. CHARACTERS A white or almost white. by interpolation. Record the flow time. between the two marks on the viscometer.0 ml of 1M cupriethylenediamine hydroxide solution. where k1 is the viscometer constant.9). insert the stopper and shake until completely dissolved. t1. powdered).0 ml of the solution to a suitable capillary viscometer (2. Equilibrate the solution at 25±0. in acetone.aspx . where k2 is the viscometer constant. fine or granular powder. Dilute a suitable volume of 1M cupriethylenediamine hydroxide solution with an equal volume of water R and measure the flow time. with mineral acids. Determine the relative viscosity hRel of the substance to be examined using the formula: h1/h2.300 g to a 125 ml conical flask. (1) IDENTIFICATION A. Calculate the kinematic viscosity n2 of the solvent using the formula: t2(k2). DEFINITION Microcrystalline cellulose is a purified. Calculate the degree of polymerisation P using the formula: 28 Contact :: info@icpc. obtained as a pulp from fibrous plant material. B.0 ml of water R and 25.2. in ethanol. Add 25. t2. [h]c.biz Website :: http://icpc. Calculate the kinematic viscosity n1 of the solution using the formula: t1(k1). in seconds.1°C for not less than 5 min.

32). not allowing the temperature to exceed 800°. Cool and add to the filtrate 0.1 ml of phenolphthalein solution and 13. Not more than 6. 29 Contact :: info@icpc.2 ml of thioacetamide reagent.8). adding 4 ml of a 25% w/v solution of magnesium sulphate in 1M sulphuric acid and beginning at the words 'Mix with a fine glass rod…'. Mix using a fine glass rod and heat cautiously. (5) Water-soluble substances Shake 5. Allow to cool. 20 min and (4) Ether-soluble substances Prepare a column using 10. Prepare the standard using 2 ml of lead standard solution (10 ppm Pb) R. and continue heating until a white or at most greyish residue is produced. TESTS (2) Solubility Dissolve 50 mg in 10 ml of ammoniacal solution of copper tetrammine R. add to 1. Pass 50 ml of peroxide-free ether R through the column. The pH of the supernatant liquid is 5.3). Shake 5 g with 40 ml of carbon dioxide-free water R for centrifuge. The residue weighs not more than 5. If the mixture is liquid. (6) Starch To 10 g add 90 ml of water R and boil for 5 min.2.5M ammonia dropwise until a pink colour is produced.2 ml of 1M sulphuric acid. Dissolve the residue using two 5-ml quantities of 2M hydrochloric acid. determined on 1.XYZ PHARMACEUTICAL where m is the mass in grams. evaporate gently to dryness on a water bath.8) Test C Place the prescribed quantity (usually not more than 2 g) of the substance being examined in a silica crucible with 4 ml of a 25% w/v solution of magnesium sulphate in 1M sulphuric acid.5. Cool.05M iodine. ignite again and allow to cool. add glacial acetic acid until the solution is decolorised and add a further 0. Filter with the aid of vacuum into a tared flask.0 g with 80 ml of water R for 10 min.4. Method: (2.biz Website :: http://icpc. (7) Heavy metals (2. Progressively heat to ignition. It dissolves completely. Add 0.5 mg (0. 2. evaporate. Any brown colour produced is not more intense than that obtained by treating in the same manner a mixture of 2 ml of the test solution obtained above and 10 ml of the 20 ml of solution obtained by repeating the procedure using the prescribed volume of lead standard solution (10 ppm Pb) in place of the substance being examined. The degree of polymerisation is not more than 350.biz/PharmaceuticalDossier. mix immediately and allow to stand for 2 minutes.0 g in a tube about 20 mm in internal diameter. Evaporate to dryness on a water-bath and dry at 100°C to 105°C for 1 h. of the substance to be examined and b is the loss on drying as a percentage. No blue colour is produced. The residue weighs not more than 12. The standard solution exhibits a slightly brown colour when compared to a solution prepared by treating in the same manner a mixture of 10 ml of water and 2 ml of the solution being examined. Filter whilst hot.1 ml of 0.05 per cent). Filter if necessary and dilute the solution to 20 ml with water. mix.aspx .5 ml. To 12 ml of the resulting solution add 2 ml of acetate buffer pH 3.5.0 g complies with limit test C for heavy metals (10 ppm). leaving no residue.4.0.0 mg (0. The total period of ignition must not exceed 2 hours. to 7.25 per cent). Evaporate the eluate to dryness. (3) pH (2. moisten the residue with 0.2.0 g by drying in an oven at 100°C to 105°C for 3 h. (8) Loss on drying (2.0 per cent.

4.aspx . (e) Under high vacuum The drying is carried out over phosphorus pentoxide at a pressure not exceeding 0.6. weigh. for Staphylococcus aureus and for Salmonella (2. (2. (c) In vacuo within a specified temperature range The drying is carried out over phosphorus pentoxide at a pressure of 1. for Pseudomonas aeruginosa. non-mucoid colonies of Gram-negative rods indicates the possible presence of E. Allow to cool.14).12) and use 10 ml or the quantity corresponding to 1 g or 1 ml to inoculate 100 ml of broth medium A.4. determined on 1. determined by plate-count. (d) In an oven within a specified temperature range The drying is carried out in an oven within the temperature range specified in the monograph.6.12) not more than 103 microorganisms per gram and with a limit for fungi of 102 per gram. Shake the container. (9) Sulphated ash (2. then cautiously over a flame and then progressively to about 600°. (a) In a desiccator The drying is carried out over phosphorus pentoxide at atmospheric pressure and at room temperature. the procedure to be used is described in full in the individual monograph. (b) In vacuo The drying is carried out over phosphorus pentoxide at a pressure of 1. Place a suitable quantity of the substance being examined. Continue incineration until all black particles have disappeared and then allow to cool.5 to 2.0 g.biz/PharmaceuticalDossier.XYZ PHARMACEUTICAL Method (2.13).biz Website :: http://icpc.14) Heat a silica or platinum crucible to redness for 30 minutes.6. Growth of red. 30 Contact :: info@icpc. evaporate to dryness and incinerate carefully. such as indole production. coli.5 to 2. Method: (2.13) Escherichia coli Prepare the product to be examined as described in the general method Appendix XVI B2 (2. (10) Microbial contamination Total viable aerobic count (2. Dry the substance to constant weight or for the prescribed time by one of the following procedures.2. This is confirmed by suitable biochemical tests. homogenise and incubate at 35° to 37° for 18 to 48 hours. Add a few drops of 1M sulphuric acid. add 2 ml of 1M sulphuric acid and heat. Not more than 0. transfer 1 ml to 100 ml of broth medium G and incubate at 43° to 45° for 18 to 24 hours. If other conditions are prescribed.6.1 kPa at the temperature prescribed in the monograph.1 per cent.32) Place the prescribed quantity of the substance being examined in a weighing bottle previously dried under the conditions prescribed for the substance being examined. Subculture on plates of agar medium H at 35° to 37° for 18 to 72 hours.5 kPa at room temperature. It complies with the tests for Escherichia coli. in the crucible. incinerate as before and allow to cool.5 kPa within the temperature range specified in the monograph. Add a few drops of a 15. The product passes the test if such colonies are not seen or if the confirmatory biochemical tests are negative. incinerate for 15 minutes and repeat this procedure to constant weight.8% w/v solution of ammonium carbonate. allow to cool in a desiccator and weigh. first on a water bath.

Pseudomonas aeruginosa Prepare the product to be examined as described in the general method Appendix XVI B2 (2. Black colonies of gram-positive cocci.0. 31 Contact :: info@icpc. Subculture on at least two different agar media chosen from agar medium J. red colonies. Subculture on a plate of agar medium N and incubate at 35° to 37° for 18 to 72 hours. When testing transdermal patches. often surrounded by a pink or red zone. homogenise and incubate at 35° to 37° for 18 to 24 hours.6. Incubate at 35° to 37° for 18 to 72 hours. transfer some material of morphologically different. Precise confirmation may be carried out by appropriate biochemical and serological tests.12). Staphylococcus aureus Prepare the product to be examined as described in the general method Appendix XVI B2 (2. The product passes the test if no growth occurs at 41° to 43°. colourless or pink or opaque-white colonies.6. with or without black centres. Confirmation may be effected by suitable biochemical tests such as the coagulase test and the deoxyribonuclease test.6.biz Website :: http://icpc. Transfer separately a few of the suspect colonies to agar medium M in tubes.6.aspx . After incubation spread on agar medium N. Subculture on a plate of agar medium O and incubate at 35° to 37° for 18 to 72 hours. with or without production of hydrogen sulphide in the agar.12) and use 10 ml or the quantity corresponding to 1 g or 1 ml to inoculate 100 ml of broth medium A. The product passes the test if colonies of the type described do not appear or if the confirmatory biochemical and serological tests are negative. The product passes the test if colonies of the type described do not appear on agar medium O or if the confirmatory biochemical tests are negative. agar medium L: small. If growth of gram-negative rods occurs. The presence of salmonellae is provisionally confirmed if in the deep inoculation but not in the surface culture there is a change of colour from red to yellow and usually a formation of gas. surrounded by a clear zone indicate the presence of S.XYZ PHARMACEUTICAL Salmonella Prepare the product to be examined as described in the general method Appendix XVI B2 (2. but using broth medium A in place of buffered sodium chloride-peptone solution pH 7. agar medium K and agar medium L. aureus. homogenise and incubate at 35° to 37° for 18 to 48 hours. transparent. The probable presence of salmonellae is indicated by the growth of cultures having the following appearance: agar medium J: agar medium K: well-developed. homogenise and incubate at 35° to 37° for 18 to 48 hours. colourless colonies. the product passes the test.12) through a sterile filter membrane and place in 100 ml of broth medium A and incubate at 35° to 37° for 18 to 48 hours. Transfer 1 ml of the enrichment culture to 10 ml of broth medium I and incubate at 41° to 43° for 18 to 24 hours. filter 50 ml of preparation A as described in the general method Appendix XVI B2 (2. If no growth of microorganisms is detected. using surface and deep inoculation. well-developed. isolated colonies to broth medium A and incubate at 41° to 43° for 18 to 24 hours.12) and use 10 ml or the quantity corresponding to 1 g or 1 ml to inoculate 100 ml of broth medium A.biz/PharmaceuticalDossier.

filter 50 ml of preparation A as described in the general method Appendix XVI B2 (2. Total viable aerobic count (2. Proceed as follows.biz Website :: http://icpc. in tubes containing suitable media such as those indicated. POUR-PLATE METHOD Using Petri dishes 9 cm in diameter. Dilute portions of each of the cultures using buffered sodium chloride-peptone solution pH 7. Nutritive and selective properties of the media and validity of the test The tests described hereafter must be performed at least on each lot of dehydrated media.39).0 to make test suspensions containing about 1000 viable micro-organisms per millilitre.6. or 15 ml to 20 ml of a liquefied agar medium suitable for the cultivation of fungi (such as medium C) at not more than 45°. 32 Contact :: info@icpc. may also be used): broth medium A.aspx . aeruginosa.XYZ PHARMACEUTICAL When testing transdermal transdermal patches.12) Plate count methods A. Pseudomonas aeruginosa A Escherichia coli such as ATCC 9027 (NCIMB 8626. aureus. Select the plates corresponding to one dilution and showing the highest number of colonies less than 300 (100 colonies for fungi). such as Salmonella abony (NCTC 6017. A positive result for the respective microorganisms must be obtained. CIP 80.6. coli and Salmonellae in the presence and in the absence of the product to be examined.12) through a sterile filter membrane and place in 100 ml of broth medium A and incubate at 35° to 37° for 18 to 48 hours. E.83): broth medium A. After incubation spread on agar medium O. Mix equal volumes of each suspension and use 0. Ps.118): broth medium such as ATCC 8739 (NCIMB 8545.126): broth medium A Salmonella typhimurium no strain number is recommended (a salmonella not pathogenic for man. Prepare for each medium at least two Petri dishes for each level of dilution. CIP 82. at 30° to 35° for 18 to 24 hours: Staphylococcus aureus such as ATCC 6538 (NCIMB 9518.biz/PharmaceuticalDossier. If larger Petri dishes are used the amount of agar is increased accordingly. Grow the following test strains separately. CIP 4. CIP 53. Incubate the plates at 30° to 35° (20° to 25° for fungi) for five days.4 ml (approximately 100 micro-organisms of each strain) as an inoculum in tests for S. add to each dish 1 ml of the sample prepared as described in the section 'Preparation of the sample' and 15 ml to 20 ml of a liquefied agar medium suitable for the cultivation of bacteria (such as medium B). Take the arithmetic average of the counts and calculate the number of colony-forming units per gram or millilitre. unless a reliable count is obtained in a shorter time.

IDENTIFICATION First identification: C. A. The retention times of the principal peaks in the chromatogram obtained with the test solution are approximately the same as those of the principal peaks in the chromatogram obtained with the reference solution. B. 20 ml of dilute nitric acid R and 20 ml of distilled water R and heat under a reflux condenser until 33 Contact :: info@icpc. It contains not less than 4. 591. practically insoluble in water and in ethanol.biz Website :: http://icpc.3] and palmitic acid [(C15H31COO)2Mg. very fine. TESTS Solution S: To 5. The residue obtained in the preparation of solution S has a freezing point not lower than 53°C. CHARACTERS A white.30). Second identification: A. light powder.1] and in minor proportions other fatty acids.0 g add 50 ml of peroxide-free ether R.0 per cent of stearic acid and the sum of stearic acid and palmitic acid is not less than 90.biz/PharmaceuticalDossier. 535.0 per cent.XYZ PHARMACEUTICAL Name of Material Tested as per Magnesium Stearate BP BRITISH PHARMACOPEIA DEFINITION Magnesium stearate is a mixture of magnesium salts of different fatty acids consisting mainly of stearic acid [(C17H35COO)2Mg. C. Examine the chromatograms obtained in the test for fatty acid composition. The fatty acid fraction contains not less than 40.200 g of the residue obtained in the preparation of solution S dissolved in 25 ml of the prescribed mixture of solvents. D. 1 ml of solution S gives the reaction of magnesium. D.0 per cent of Mg (Ar 24. greasy to the touch.aspx . calculated with reference to the dried substance. D. B. determined on 0. The acid value of the fatty acids is 195 to 210.0 per cent and not more than 5.

Test solution. determined by atomic absorption spectrometry. Measure the absorbance at 228. Cadmium: Not more than 3 ppm of Cd. diluted if necessary with a 1 per cent V/V solution of hydrochloric acid R. each of 4 ml. Prepare the reference solutions using cadmium standard solution (10 ppm Cd) R.0 ml with the same solvent.05 ml of bromothymol blue solution R1.5 per cent). Lead: Not more than 10 ppm of Pb. Allow to digest at 170°C for 5 h. Allow to cool. wash with 15 ml of peroxide-free ether R and dilute to 50 ml with distilled water R (solution S).5 ml of 0. separate the aqueous layer and shake the ether layer with two quantities. Chlorides: 0. Test solution. 34 Contact :: info@icpc. Combine the aqueous layers.0 g add 20 ml of carbon dioxide-free water R and boil for 1 min with continuous shaking.01M sodium hydroxide is required to change the colour of the indicator. Sulphates: 0. In a separating funnel.3 ml of solution S diluted to 15 ml with distilled water R complies with the limit test for sulphates (0.XYZ PHARMACEUTICAL Name of Material Tested as per Magnesium Stearate BP BRITISH PHARMACOPEIA dissolution is complete. Dissolve the residue in water R and dilute to 5. Allow to cool. Use the solution described in the test for cadmium.01M hydrochloric acid or 0. Keep the residue for identification A and B. determined by atomic absorption spectrometry. Cool and filter.biz/PharmaceuticalDossier.aspx .0 mg of the substance to be examined in a polytetrafluoroethylene digestion bomb and add 0.8 nm. Not more than 0. Place 50.5 ml of a mixture of 1 volume of hydrochloric acid R and 5 volumes of cadmium. Reference solutions. of distilled water R.and lead-free nitric acid R. Acidity or alkalinity: To 1.1 per cent). To 10 ml of the filtrate add 0.5 ml of solution S diluted to 15 ml with water R complies with the limit test for chlorides (0. using a cadmium hollow-cathode lamp as a source of radiation and an air-acetylene flame. Evaporate the organic layer to dryness and dry the residue at 100°C to 105°C.biz Website :: http://icpc.

biz/PharmaceuticalDossier. Carry out a blank titration. Heat to 45°C to 50°C until the solution is clear and titrate with 0.0 nm. 1 ml of 0. 5 ml of concentrated ammonia R. Use the solution described in the test for cadmium.250 g in a 250 ml conical flask add 50 ml of a mixture of equal volumes of butanol R and ethanol R.XYZ PHARMACEUTICAL Name of Material Tested as per Magnesium Stearate BP BRITISH PHARMACOPEIA Reference solutions. 35 Contact :: info@icpc.aspx . determined by atomic absorption spectrometry.biz Website :: http://icpc. Reference solutions.000 g by drying in an oven at 100°C to 105°C. diluted if necessary with water R. Fatty acid composition: Examine by gas chromatography. depending on the apparatus the line at 217. Microbial contamination: Total viable aerobic count not more than 103 micro-organisms per gram.0 ml of 0. using a nickel hollow-cathode lamp as a source of radiation and an air-acetylene flame. 3 ml of ammonium chloride buffer solution pH 10. ASSAY Magnesium: To 0.0 R.3 nm. using a lead hollow-cathode lamp as a source of radiation and an air-acetylene flame. It complies with the test for Escherichia coli). determined by plate count. diluted if necessary with water R.431 mg of Mg. Measure the absorbance at 232. Test solution.1M sodium edetate and 15 mg of mordant black 11 triturate R.0 per cent.1M zinc sulphate until the colour changes from blue to violet. Prepare the reference solutions using nickel standard solution (10 ppm Ni) R.0 nm may be used. 30. Prepare the reference solutions using lead standard solution (10 ppm Pb) R.1M sodium edetate is equivalent to 2. determined on 1. Measure the absorbance at 283. Nickel: Not more than 5 ppm of Ni. Loss on drying: Not more than 6.

with the following temperature programme: Inject 1 µl of the reference solution.0 ml with heptane R.88.XYZ PHARMACEUTICAL Name of Material Tested as per Magnesium Stearate BP BRITISH PHARMACOPEIA Test solution. When the chromatograms are recorded in the prescribed conditions. disregarding the peak due to the solvent.32 mm in internal diameter coated with macrogol 20.0. Reference solution.4 ml/min. The chromatographic procedure may be carried out using: — a fused-silica column 30 m long and 0. STORAGE Store in a well-closed container. a flame-ionisation detector.0 ml of the solution to 100. Allow to cool.0 mg of palmitic acid CRS and 50. Remove about 2 ml of the organic layer and dry over 0. dissolve 0. Inject 1 µl of the test solution. in the chromatogram obtained with the reference solution.10 g of the substance to be examined in 5 ml of boron trifluoride-methanol solution R. Prepare the reference solution in the same manner as the test solution using 50. 36 Contact :: info@icpc. In a conical flask fitted with a reflux condenser.biz/PharmaceuticalDossier.2 g of anhydrous sodium sulphate R. The test is not valid unless.000 R (film thickness 0.5 µm). Dilute 1.0 mg of stearic acid CRS instead of magnesium stearate.biz Website :: http://icpc. Shake and allow the layers to separate.aspx . Boil under a reflux condenser for 10 min. Add 20 ml of a saturated solution of sodium chloride R. the retention time of methyl palmitate relative to that of methyl stearate is about 0. Calculate the percentage content of stearic acid and palmitic acid from the areas of the peaks in the chromatogram obtained with the test solution by the normalisation procedure. the resolution between the peaks corresponding to methyl stearate and methyl palmitate is at least 5. — — helium for chromatography R as the carrier gas at a flow rate of 2. Add 4 ml of heptane R through the condenser and boil again under a reflux condenser for 10 min.

To 5 ml of the gel obtained in identification test B add 0. free-flowing powder. the granules show a distinct black cross intersecting at the hilum. CHARACTERS A white or almost white. or rounded.5 g in a silica or platinum crucible and add 2 ml of a 250 g/l solution of sulphuric acid R. 30 µm to 100 µm in size. Keep the gel for the tests for appearance of gel and pH. calculated with reference to the substance washed with alcohol (80 per cent V/V) and dried. then cautiously over a naked 37 Contact :: info@icpc. partly O-carboxymethylated starch.05 ml of iodine solution R1. very hygroscopic. compound granules consisting of two to four components occur occasionally.aspx . It contains not less than 2. IDENTIFICATION A. the granules have an eccentric hilum and clearly visible concentric striations.XYZ PHARMACEUTICAL Name of Material Tested as per Sodium Starch Glycollate (Type C) BP BRITISH PHARMACOPEIA DEFINITION Sodium starch glycollate (type C) is the sodium salt of a cross-linked by physical dehydration. soluble in water.0 g and 20 ml of carbon dioxide-free water R. TESTS Solution S Place 2.biz/PharmaceuticalDossier. Solution S gives reaction (a) of sodium.8 per cent and not more than 5. practically insoluble in methylene chloride. Add 100 ml of carbon dioxide-free water R and shake: the gel remains stable (difference from types A and B).0 per cent of Na (Ar 22. irregularly shaped. 10 µm to 35 µm in size. The granules show considerable swelling in contact with water. C.99).biz Website :: http://icpc. between crossed nicol prisms. A dark blue colour is produced. The mixture has the appearance of a gel. It complies with the test for pH . It gives a translucent gel-like product in water. D. fine. Mix with shaking and without heating 4. B. ovoid or pear-shaped. small crystals are visible at the surface of the granules. Examined under a microscope it is seen to consist of granules. Heat on a water-bath.

XYZ PHARMACEUTICAL

Name of Material Tested as per Sodium Starch Glycollate (Type C) BP BRITISH PHARMACOPEIA

flame, raising the temperature progressively, and then incinerate in a muffle furnace at 600±25°C. Continue heating until all black particles have disappeared. Allow to cool, add a few drops of sulphuric acid R and heat and incinerate as described above. Allow to cool, add a few drops of ammonium carbonate solution R, evaporate to dryness and incinerate cautiously. Allow to cool and dissolve the residue in 50 ml of water R. Appearance of gel The gel prepared under identification test B is colourless . pH The pH of the gel prepared under identification test B is 5.5 to 7.5. Sodium glycollate Carry out the test protected from light. Test solution. Place 0.20 g of the substance to be examined in a beaker. Add 5 ml of acetic acid R and 5 ml of water R. Stir until dissolution is complete (about 10 min). Add 50 ml of acetone R and 1 g of sodium chloride R. Filter through a fast filter paper impregnated with acetone R, rinse the beaker and filter with acetone R. Combine the filtrate and washings and dilute to 100.0 ml with acetone R. Allow to stand for 24 h without shaking. Use the clear supernatant liquid. Reference solution. Dissolve 0.310 g of glycollic acid R, previously dried in vacuo over diphosphorus pentoxide R, in water R and dilute to 250.0 ml with the same solvent. To 5.0 ml of this solution, add 5 ml of acetic acid R and allow to stand for about 30 min. Add 50 ml of acetone R and 1 g of sodium chloride R and dilute to 100.0 ml with acetone R. Heat 2.0 ml of the test solution on a water-bath for 20 min. Cool to room temperature and add 20.0 ml of 2,7-dihydroxynaphthalene solution R. Shake and heat on a water-bath for 20 min. Cool under running water, transfer to a volumetric flask and dilute to 25.0 ml with sulphuric acid R, maintaining the flask under running water. Within 10 min, measure the absorbance at 540 nm using water R as the compensation liquid. The absorbance of the solution prepared with the test solution is not greater than that of a solution prepared at the same time and in the same manner with 2.0 ml of the reference solution (2.0 per cent). Sodium chloride Not more than 1 per cent. Shake 1.00 g with 20 ml of alcohol (80 per cent V/V) R for 10 min and filter. Repeat the operation four times. Dry the residue to constant mass at 100°C and set aside for the assay. Combine the filtrates. Evaporate to dryness, take up the residue with water R and dilute to 25.0 ml with the same solvent. To 10.0 ml of the solution add 30 ml of water R

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XYZ PHARMACEUTICAL

Name of Material Tested as per Sodium Starch Glycollate (Type C) BP BRITISH PHARMACOPEIA

and 5 ml of dilute nitric acid R. Titrate with 0.1M silver nitrate, determining the end-point potentiometrically , using a silver indicator electrode. 1 ml of 0.1M silver nitrate is equivalent to 5.844 mg of NaCl. Iron 10 ml of solution S complies with the limit test for iron (20 ppm). Heavy metals 1.0 g complies with limit test D for heavy metals (20 ppm). Prepare the standard using 2 ml of lead standard solution (10 ppm Pb) R. Loss on drying Not more than 7.0 per cent, determined on 1.000 g by drying in an oven at 100°C to 105°C for 4 h. Microbial contamination It complies with the test for Escherichia coli and Salmonella . ASSAY To 0.250 g of the dried and crushed residue obtained in the test for sodium chloride add 80 ml of anhydrous acetic acid R and heat under a reflux condenser for 2 h. Cool the solution to room temperature. Titrate with 0.1M perchloric acid, determining the end-point potentiometrically. Carry out a blank test. 1 ml of 0.1M perchloric acid is equivalent to 2.299 mg of Na. STORAGE Store in an airtight container, protected from light.

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XYZ PHARMACEUTICAL

Name of Material Tested as per Molecular Formula:SiO2 Mol. Wt. 60.08

COLLOIDAL SILICON DIOXIDE USP

Category: Pharmaceutical aid (tablet excipient). Description: Light, fine, white, amorphous powder. It has a particle size of about 15 nm. Solubility: Practically insoluble in water and in mineral acids with the exception of hydrofluoric acid. Dissolves in hot solutions of alkali hydroxides. When 1 g is shaken vigorously with 20 ml of carbon tetrachloride for 3 minutes; a transparent gel is produced. STANDARDS Colloidal Silicon Dioxide contains not less than 99.0 per cent and not more than 100.5 per cent of SiO2, calculated with reference to the ignited substance. Identification: About 20 mg gives the reaction of silicates. pH: Between 3.5 and 5.5, determined in a suspension of 1 g in 30 ml of carbon dioxide-free water. Chloride: To 1.0 g add a mixture of 20 ml of 2M nitric acid and 30 ml of water, heat on a water-bath for 15 minutes, shaking frequently, dilute to 50 ml with water if necessary, filter and cool. The filtrate complies with the limit test for chlorides. (250 ppm). Arsenic: To 2.5 g contained in a round-bottomed flask add 50 ml of 3M hydrochloric acid and heat under a reflux condenser for 30 minutes. Cool, filter with the aid of suction and transfer the filtrate to a 100-ml volumetric flask. Wash the filter with several portions of hot water and add the washings to the volumetric flask. Cool, dilute to volume with water and mix. To 50.0 ml of the solution add 3 ml of hydrochloric acid; the resulting solution complies with the limit test for arsenic, (8 ppm). Heavy metals: Not more than 25 ppm, determined by Method D on 12 ml of a solution prepared in the following manner. Suspend 2.5 g in sufficient water to produce a semi-fluid slurry and dry at 140o. When the dried substance is white, break up the mass using a glass rod, add 25 ml of 1M hydrochloric acid, boil gently for 5 minutes, stirring frequently with the glass rod, centrifuge for 20 minutes and filter the supernatant liquid through a membrane filter. To the residue in the centrifuge tube add 3 ml of 2M hydrochloric acid and 9 ml of water, boil, centrifuge for 20 minutes and filter the

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To 20. combine the filtrates and washings and dilute to 50. Loss on ignition: Not more than 5.0%. avoiding loss from sputtering. Wash the sides of the dish with 6 ml of hydrofluoric acid.2 ml of sulphuric acid and sufficient ethanol (95%) to moisten the residue completely. 41 Contact :: info@icpc. add 6 ml of hydrofluoric acid and evaporate to dryness on a hot plate at 95o to 105o. evaporate to dryness in a well-ventilated hood. The difference between the weight of the final residue and that of the residue obtained in the test for Loss on ignition represents the amount of SiO2 in the amount of the substance taken for the test for Loss on ignition.aspx . ignite at 1000o. Wash the residue with small quantities of water. neutralise with 2M ammonia and dilute to 25 ml with water. determined on 0. Use lead standard solution (1 ppm Pb) to prepare the standard.0 ml of the solution add 50 mg of L-ascorbic acid and 1 ml of strong ammonia solution. allow to cool in a desiccator and weigh.0 ml with water.XYZ PHARMACEUTICAL Name of Material Tested as per COLLOIDAL SILICON DIOXIDE USP supernatant liquid through the same membrane filter.biz Website :: http://icpc.2 g by igniting at 900o in a platinum crucible for 2 hours Assay: To the residue obtained in the test for Loss on ignition add 0.biz/PharmaceuticalDossier.

at 1018 ± 2 cm-1 and at 669 ± 2 cm-1. Allow to cool and transfer the melted mass into an evaporating dish with 50 ml of hot water R. selected.0 g of potassium carbonate R. Pure talc has the formula [Mg3Si4O10(OH) 2. Second identification: B. Add 10 ml of hydrochloric acid R and evaporate to dryness on a water-bath. retaining as much as possible of the insoluble material in the beaker. homogeneous. Examine the substance as discs prepared using potassium bromide R. crystalline precipitate is formed.biz Website :: http://icpc.0 g of the substance to be examined into a conical flask fitted with a reflux condenser.aspx . The spectrum shows absorption bands at 3677 ± 2 cm-1. greasy to the touch (non abrasive). Examine by infrared absorption spectrophotometry.biz/PharmaceuticalDossier. Transfer the mixture to a beaker and allow the undissolved material to settle. CHARACTERS A light. Filter the supernatant through medium-speed filter paper into a 100 ml volumetric flask.2 g of anhydrous sodium carbonate R and 2. hydrated magnesium silicate. natural. A. magnesite (magnesium carbonate). To the melted mass add 0. IDENTIFICATION First identification: A. calcite (calcium carbonate) and dolomite (calcium and magnesium carbonate) are predominant. The residue obtained in identification test B gives the reaction of silicates. practically insoluble in water.XYZ PHARMACEUTICAL Name of Material Tested as per DEFINITION Talc is a powdered. C. in alcohol and in dilute solutions of acids and alkali hydroxides. B. Allow to cool.5M hydrochloric acid gradually while stirring and heat on a water-bath for 30 min. To 5 ml of the filtrate add 1 ml of ammonia R and 1 ml of ammonium chloride solution R and filter. heat to boiling and filter. In a platinum crucible. A white. add 50 ml of 0. Mr 379. TESTS Solution S1: Weigh 10. Add 20 ml of water R. It may contain variable amounts of associated minerals among which chlorites (hydrated aluminium and magnesium silicates). C. (The residue is used for identification test C).1 g of the substance to be examined and heat until the mixture is completely melted. Allow to cool. Wash the residue and the beaker with three Purified Talc BP BRITISH PHARMACOPEIA 42 Contact :: info@icpc. white or almost white powder. Add hydrochloric acid R until effervescence ceases. melt a mixture of 0. To the filtrate add 1 ml of disodium hydrogen phosphate solution R.3].

Stir gently then add 35 ml of hydrofluoric acid R and evaporate slowly to dryness on a hot plate.0 ml of hydrochloric acid R and 10 ml of lanthanum chloride solution R. heat to boiling and maintain boiling under a reflux condenser for 30 min.0 g add 50 ml of carbon dioxide.acetylene flame.0 ml of aluminium standard solution (100 ppm Al) R and dilute to 100. Reference solutions. To the residue.0 ml with the same solvent. add 5 ml of hydrochloric acid R.0. of hot water R. Take 25. heat to boiling and allow to cool. introduce respectively 43 Contact :: info@icpc.0 ml of hydrochloric acid R.0 ml with carbon dioxide-free water R.XYZ PHARMACEUTICAL Name of Material Purified Talc BP Tested as per BRITISH PHARMACOPEIA quantities. Solution S2: Weigh 0.0 per cent of aluminium. Calcium: Not more than 0. To 5.0 ml of the filtrate.34 g/l solution of caesium chloride R.biz Website :: http://icpc. 10 ml of lanthanum chloride solution R and dilute to 100. Wash the filter with 15 ml of hot water R.0 ml of hydrochloric acid R and 10 ml of a 25. Into four identical volumetric flasks. allow the filtrate to cool and dilute to 100. Test solution. 15. Test solution. pH: The pH of the filtrate obtained in the test for water.soluble substances. rinse the dish with water R and dilute to 50. Rinse the watch-glass and the dish with water R. introduce respectively 5. The residue weighs not more than 10 mg (0.0 ml.free water R. each of 10 ml.0 ml of hydrochloric acid R and dilute to 100. Read the pH 1 min after inserting the electrode. 10.0 ml. Measure the absorbance at 309.0 to 9. each containing 10.34 g/l solution of caesium chloride R. and 5 ml of perchloric acid R.34 g/l solution of caesium chloride R. Into four identical volumetric flasks.0 ml with water R.0 ml with water R. filter through a medium-speed filter paper and dilute to 50.0 ml with water R.9 per cent of calcium.2 per cent).cathode lamp as the radiation source and a nitrous oxide.0 ml and 20. Aluminium: Not more than 2.biz/PharmaceuticalDossier. Reference solutions. each containing 10. add 5 ml of hydrochloric acid R. determined by atomic absorption spectrometry. evaporate to dryness and heat at 105°C for 1 h. Water-soluble substances: To 10.aspx . determined by atomic absorption spectrometry. is 7. 5 ml of lead-free nitric acid R. using an aluminium hollow.0 ml with the same solvent. cover with a watch-glass. To 5. Allow to cool.5 g of the substance to be examined in a 100 ml polytetrafluoroethylene dish. Transfer into a volumetric flask containing 5 ml of a 25.0 ml of solution S2 add 10 ml of a 25. 10.0 ml of solution S2 add 10.3 nm.

0 per cent to 19.2 nm using a magnesium hollow. Measure the absorbance at 285.0 ml of hydrochloric acid R and 10 ml of lanthanum chloride solution R. introduce respectively 5.biz/PharmaceuticalDossier.0 ml. To 2. 2.0 ml with water R. each containing 50. 4. Measure the absorbance at 422. 44 Contact :: info@icpc. To 4.aspx . 3.5 ml. determined by atomic absorption spectrometry. determined by atomic absorption spectrometry. introduce respectively 2. Iron: Not more than 0.7 nm using a calcium hollow.0 ml with water R.0 ml of magnesium standard solution (10 ppm Mg) R1 and dilute to 100. 3. Lead: Not more than 10 ppm of lead.5 ml.0 ml. each containing 50.5M hydrochloric acid. 10.0 ml of calcium standard solution (100 ppm Ca) R1 and dilute to 100.biz Website :: http://icpc. 2.cathode lamp as the radiation source and a nitrous oxide. 7.0 ml and 12.25 per cent of iron. Measure the absorbance at 248.0 ml and 4.5 ml.5M hydrochloric acid and dilute to 100.0 ml and 5. Reference solutions.0 ml with water R.5 ml of solution S2 to 100. Dilute 0.0 ml with water R.0 ml of the solution.cathode lamp as the radiation source and an air-acetylene flame. introduce respectively 2. Magnesium 17. Make a correction using a deuterium lamp.0 ml of 0.0 ml.0 ml with water R. Use solution Sl.0 ml.0 ml of 0.0 ml and 4.0 ml.0 ml with water R. Into four identical volumetric flasks.0 ml of 0. 3. 10 ml of lanthanum chloride solution R and dilute to 100.3 nm using an iron hollow-cathode lamp as the radiation source and an air-acetylene flame.5 per cent of magnesium.0 ml of hydrochloric acid R. add 50.5 ml of lead standard solution (10 ppm Pb) R1 and dilute to 100.acetylene flame. add 10. Into four identical volumetric flasks. determined by atomic absorption spectrometry.0 ml with water R.0 ml of iron standard solution (250 ppm Fe) R and dilute to 100.5 ml of solution S1. Into four identical volumetric flasks. Reference solutions.5M hydrochloric acid. Test solution. Test solution. each containing 10. Reference solutions.XYZ PHARMACEUTICAL Name of Material Purified Talc BP Tested as per BRITISH PHARMACOPEIA 1. Test solution.

XYZ PHARMACEUTICAL Name of Material Tested as per Purified Talc BP BRITISH PHARMACOPEIA Measure the absorbance at 217.aspx . the total viable aerobic count is not more than a total of 103 aerobic bacteria and not more than 102 fungi per gram. where applicable. Microbial contamination: If intended for topical administration.0 per cent. If intended for oral administration. for oral or topical 45 Contact :: info@icpc.12) is not more than a total of 102 aerobic bacteria and fungi per gram.biz/PharmaceuticalDossier. that the substance is suitable administration. determined on 1.00 g by ignition to constant weight at 1050°C to 1100°C.6.biz Website :: http://icpc. Loss on ignition: Not more than 7.0 nm using a lead hollow-cathode lamp as the radiation source and an air-acetylene flame. LABELLING The label states. the total viable aerobic count (2.

XYZ PHARMACEUTICAL Maize starch Definition Maize starch is obtained from the caryopsis of Zea mays L.biz/PharmaceuticalDossier. A thin. ■ Solubility which creaks when Practically insoluble in cold water and in alcohol. The presence of granules with cracks or irregularities on the edge is exceptional. To 10 ml of the mucilage obtained in identification test B add 0. white to slightly yellowish.biz Website :: http://icpc. Examined under a microscope.aspx . it appears as either angular polyhedral granules of irregular sizes with diameters ranging from about 2 mm to about 23 mm or as rounded or spheroidal granules of irregular sizes with diameters ranging from about 25 mm to about 35 mm. the starch granules show a distinct black cross intersecting at the hilum. boil for 1 min and cool. Suspend 1 g in 50 ml of water R. using not less than 20 x magnification and using equal volumes of glycerol R and water R. It is tasteless. 46 Contact :: info@icpc. Identification A. Characters ■ Appearance Matt. Between crossed nicol prisms. The central hilum consists of a distinct cavity or twoto five-rayed cleft and there are no concentric striations. B. cloudy mucilage is formed. very fine powder pressed between the fingers.04 ml of iodine solution RL An orange-red to dark blue colour is produced which disappears on heating. C.

0 ml of carbon dioxide-free water R for 60 s.30) Maximum 20 ppm. determined by plate count.4.4. ■ Oxidising substances (2.2. Shake 1. ■ Iron (2. It complies with the test for Escherichia coli (2.9) Maximum 10 ppm.2. 47 Contact :: info@icpc.6 per cent.biz/PharmaceuticalDossier. calculated as H202.0 per cent. Storage In an airtight container . The filtrate Complies with the limit test for iron. ■ Loss on drying (2. ■ Sulphated ash (2.aspx .5. Shake 5.3) 4.12) not more than 103 bacteria and 102 fungi per gram.XYZ PHARMACEUTICAL Tests ■ pH (2. determined on 1.32) Maximum 15.0 to 7. determined on 1.biz Website :: http://icpc. not more than traces of matter other than starch granules are present. No starch grains of any other origin are present.29) Maximum 50 ppm.5. Filter.0 g.0 g with 25. ■ Microbial contamination Total viable aerobic count (2.14) by drying in an oven at Maximum 0. ■ Foreign matter Examined under a microscope using a mixture of equal volumes of glycerol R and water R.0.6.13).000 130°Cfor90min.6. Allow to stand for 15 min.5 g with 15 ml of dilute hydrochloric acid R. ■ Sulphur dioxide (2.

XYZ PHARMACEUTICAL CONCERNING CHEMICAL.biz/PharmaceuticalDossier.biz Website :: http://icpc. PHARMACEUTICAL AND BIOLOGICAL DOCUMENTATION FOR CHEMICAL ACTIVE SUBSTANCE(S) 48 Contact :: info@icpc.aspx .

aspx . b. crystalline powder. Molecular Formula C8H9NO2 c. centrally acting analgesic derived from paminophenol. nonopiate. Light. Structural Similarities/Differences of the Drug to Other Available Compounds or Groups of Compounds Acetaminophen is a synthetic.biz Website :: http://icpc. Solubility water 1:70 boiling water 1:20 alcohol 1:10 chloroform 1:50 glycerin 1:40 ether slightly soluble Chemical Properties a. and Moisture 49 Contact :: info@icpc. pKa The pKa of acetaminophen is 9. c. Structural Formula b.XYZ PHARMACEUTICAL DRUG DESCRIPTION Generic Name PARACETAMOL TABLET (Acetaminophen) Physical Properties Of The Chemical Entity1 a. The full chemical name is N-acetyl-p-aminophenol.16 d. Stability of the Drug to Temperature. Molecular Weight 151. Macroscopic Appearance Acetaminophen is a white.51 at 25°C. e.biz/PharmaceuticalDossier.

XYZ PHARMACEUTICAL Acetaminophen is stable to temperature. all rights reserved. or dissolved in a liquid. or cups that come with other medicines. PA: Mack Publishing Company.. Copyright© 1985. and moisture. such as spoons. Inc. such as kitchen teaspoons. 50 Contact :: info@icpc.biz/PharmaceuticalDossier. children's suspension) has a pH of 5. f. PARACETAMOL Arthritis Extended Relief Caplets should not be crushed. light. 1995:1109-1110. pH Range Over Which Drug is Stable in Solution Acetaminophen is stable at a pH between 4 and 7 at 25°C. Bethesda. Inc. They are available in a variety of convenient dosage forms as listed in Tables 2 and 3. osmolarity of the PARACETAMOL acetaminophen suspension products cannot be determined.8 to 6. Remington's Pharmaceutical Sciences. Easton.aspx . or cups that come with other medicines. elixir.biz Website :: http://icpc. pH of Commercially Available Liquid Products Acetaminophen oral solution (ie. adult liquid) has a pH of 3. infants' drops. d. 23rd ed. *Permission to use the Product Information Form for the American Hospital Formulary Service as modified by McNeil Consumer Healthcare has been granted by the American Society of Health-System Pharmacists.. 7272 Wisconsin Avenue. References 1. The answers were not supplied by the Society nor are they intended to imply the endorsement of the American Society of Health-System Pharmacists.1 and the oral suspension (ie. Osmolarity/Osmolality of Commercially Available Solutions Extra Strength PARACETAMOL acetaminophen Adult Liquid: 3058 ± 152 mmol/kg Children's PARACETAMOL acetaminophen Elixir: 6040 ± 25 mmol/kg Because of the nature of suspension formulations.4 to 6. neither does the Society affirm or deny the accuracy of the answers contained herein. e. For ease of administration for young children. American Society of HealthSystem Pharmacists. chewed. Infants' f Concentrated Drops are more concentrated than the Children's PARACETAMOL liquid formulations.9. The labeling on Children's PARACETAMOL liquid formulations instructs consumers to use only the measuring cup enclosed in the package to dose the product and not to use any other dosing device. The answers to all questions are prepared and furnished by the manufacturer. droppers. INDICATIONS DOSAGE RANGE a. Administration PARACETAMOL acetaminophen products are only administered orally. MD 20814. Infants' PARACETAMOL Concentrated Drops labeling instructs consumers to use only the dropper enclosed in the carton to dose the product and not to use any other dosing device with the product. droppers.

aspx . b Doses may be repeated every 4 hours but not more than five times daily c Data not available to define appropriate adjustments. Age-Related Dosing Schedule The age-related schedule is based on standard age divisions proposed by the United States Food and Drug Administration (FDA) and used in the development of an acetaminophen dosing schedule.9 12 . the dose is 1300 mg every 8 hours as needed.9 11 years 480 2400 * Refer to package label for more specific information related to dosing. Use of antipyretics in the immediate neonatal period is extremely limited.biz Website :: http://icpc. Pediatric Dosage For children under 12 years of age. PARACETAMOL Arthritis Extended Relief Formula) are not intended for use in children under 12 years of age.10. not to exceed 4000 mg in 24 hours (Table 2). Some adult products (Extra Strength PARACETAMOL. not to exceed 3900 mg in 24 hours.9 9-10 years 400 2000 72-95 32.0 -26.0 . Adult Dosage For adults and children 12 years of age and older. Recommended pediatric dosing of acetaminophen by weight and age (adapted from reference 47. the recommended dose of acetaminophen is 650 to 1000 mg every 4 to 6 hours as needed.4 0-3 monthsc 40 200 12 -17 5.5. otherwise.9 4-5 years 240 1200 48-59 22. The weight-related schedule is based on weight ranges that are consistent with the use of a standard 80-mg dosage unit. the weight-related dosage schedule provides a dose of 10 to 15 mg/kg body weight for a single dose. if any.0 . Weight-Related Dosing Schedule This weight-related dosing schedule was developed and recommended by McNeil Consumer Healthcare when dosing by weight.47 TABLE 4. consumers should be instructed to use weight to calculate dose.7.0 .21.9 2-3 years 160 800 36-47 16.biz/PharmaceuticalDossier. the recommended dose of acetaminophen is 10 to 15 mg/kg every 4 to 6 hours.0 . not to exceed five doses in 24 hours. The weight-related schedule most closely approximates this dose.47 Using this method.0 -43.XYZ PHARMACEUTICAL b.15.47 not to exceed five doses (50-75 mg/kg) in 24 hours (Table 3). c. 51 Contact :: info@icpc. a For adults and children 12 years of age and older see Table 2.9 6-8 years 320 1600 60-71 27.5 . age may be used (Table 4). The label for Regular Strength PARACETAMOL acetaminophen products recommends that children 6 to 11 years old take 325 mg every 4 to 6 hours.23 months 120 600 24-35 11. needed for the immediate neonatal period. For extended-release acetaminophen. so that when possible.0 . with permission)* Weight Single Recommended Agea doseb (mg) daily dose (mg) lb kg 6-11 2.31.9 4-11 months 80 400 18 -23 8.

49 Williams and colleagues50 evaluated the use of acetaminophen in doses up to 2600 mg/d for up to 2 years. Williams HJ. 1983. 50.36:11961206. g. an ester of acetyl-salicylic acid and paracetamol. There are no studies to support alternate dosing of acetaminophen and ibuprofen or other nonsteroidal anti-inflammatory drugs (NSAIDs). e. Pediatric dosing of acetaminophen. 1991.aspx . Simila S. 1983. It is recommended that high humidity and excessive heat (ie. acetaminophen was well tolerated. Studies have demonstrated that single-dose concurrent administration of aspirin and acetaminophen produced a more prolonged temperature decrement than when either antipyretic was given alone. Bradley J D. The package label for Children's PARACETAMOL products instructs parents not to administer PARACETAMOL to children for pain for more than 5 days or for fever for more than 3 days unless directed by a doctor. geltabs).34:59-66. Evaluation of acetaminophen in the management of osteoarthritis of the knee.3:321-327. Brandt KD. Expiration Dating Periods for Commercially Available Products Under room temperature storage conditions. The package label for adult PARACETAMOL acetaminophen products instructs adults not to take PARACETAMOL for pain for more than 10 days or for fever for more than 3 days unless directed by a doctor. 48. Oral antipyretic therapy: evaluation of benorylate.325: 87-91. and solid formulations are as follows: store at room temperature. Arthritis Rheum. liquids. As with all over-the-counter (OTC) analgesics. Pediatr Pharmacol. 1993. PARACETAMOL acetaminophen solid formulations are generally stable for 3 years and liquid formulations are generally stable for 2 years from the date of manufacture. In these studies. et al. Curr Ther Res. Ward JR. References 47. Use of Recommended Doses for Longer Than 10 Days Clinical studies have evaluated the use of acetaminophen in adult patients with osteoarthritis of the knee at recommended doses of 4000 mg/d for up to 4 weeks. Keinanen S. Temple AR. Comparison of an antiinflammatory dose of ibuprofen.121:15-20.biz/PharmaceuticalDossier. an analgesic dose of ibuprofen. gelcaps.48. 51. Recommended Storage Conditions Storage requirements for all PARACETAMOL acetaminophen drops.51. Ryan SI. Refer to product package for specific expiration date. 52 Contact :: info@icpc. Kalasinski LA. Cummings DM. Kouvalainen K.52 f. Eur J Pediatr. 1975. Alternate/Concomitant Dosing Concomitant or alternate dosing with more than one antipyretic agent is not recommended. ≥ 40°C [104°F]) be avoided for the gelatin-coated formulations (eg. Freezing of the liquid or suspension formulations should be avoided. this warning is necessary so that patients and parents will seek appropriate medical evaluation of their condition if it persists beyond these time periods. Comparison of naproxen and acetaminophen in a two-year study of treatment of osteoarthritis of the knee. 49.biz Website :: http://icpc. Egger MJ. N Engl J Med. Katz BP.XYZ PHARMACEUTICAL d. Amadio P. and acetaminophen in the treatment of patients with osteoarthritis of the knee.

biz/PharmaceuticalDossier. Young FH. Am J Dis Child. Although some authors suggest that alcoholics may be at increased risk from therapeutic doses.138 Available data are conflicting. These data indicate that there is no increased risk from an acetaminophen overdose in patients on chronic hydantoin therapy. Shirkey HC. who overdose on acetaminophen." Chronic heavy alcohol abusers may be at increased risk of liver toxicity from excessive acetaminophen use.139 Hydantoins At usual oral therapeutic doses of acetaminophen and hydantoins. Pharmacokinetic studies indicate that phenytoin primarily induces the glucuronidation pathway. reports usually involve cases of severe chronic alcoholics and the dosages of acetaminophen most often exceed recommended doses and often involve substantial overdose.140 Additionally.111-115 Healthcare professionals should alert their patients who regularly consume large amounts of alcohol not to exceed recommended doses of acetaminophen. Anticonvulsants Some reports have suggested that patients taking long-term anticonvulsants. no special dosage adjustment or monitoring is generally required.aspx . Steele RW.biz Website :: http://icpc.108-110 Studies evaluating the metabolism of doses up to 20 mg/kg of acetaminophen in chronic alcohol abusers and a study evaluating the effects of 2 days of acetaminophen dosing at 4000 mg daily in chronic alcoholics undergoing detoxification do not support an increased risk of hepatotoxicity with recommended doses of acetaminophen. Oral antipyretic therapy: evaluation of aspirin-acetaminophen combination.123:204-206. may be at increased risk of hepatotoxicity because of accelerated metabolism of acetaminophen. SIDE EFFECTS No information provided.141 whereas acetaminophen is primarily metabolized by CYP2E1. ask your doctor whether you should take acetaminophen or other pain relievers/fever reducers. "If you consume 3 or more alcoholic drinks every day. DRUG INTERACTIONS Potential Drug-Drug Interactions Alcohol The package label for adult TYLENOL® acetaminophen products contains an alcohol warning that states. whereas glutathione-derived metabolites are not increased in patients on chronic phenytoin therapy. Bass JW.XYZ PHARMACEUTICAL 52. A 7-year retrospective study of acetaminophen overdose admissions indicates that the overall mortality rate was not significantly different for patients taking concomitant anticonvulsant medications.137. recent data demonstrate that phenytoin is metabolized primarily by CYP2C9 and CYP2C19. 53 Contact :: info@icpc. Acetaminophen may cause liver damage. 1972. although reports of this event are rare.

Carbamazepine is primarily metabolized by CYP3A4.aspx .148 Oral Anticoagulants Many factors. whereas acetaminophen is metabolized primarily via CYP2E1. any evidence suggesting increase of activity was only seen during a brief period from 12 to 48 hours after discontinuation of isoniazid.147. indicating that isoniazid could actually protect against hepatotoxicity from an acetaminophen overdose. inhibition or induction may be present following discontinuation of isoniazid therapy. caution should be used with concomitant administration of diflunisal and acetaminophen and patients should be monitored carefully. periodic evaluation of prothrombin time should be performed when these agents are administered concurrently.146. however. discontinued.147 However. In the period immediately following discharge from the hospital or whenever other medications are initiated. data from individual case reports are unclear as to whether chronic administration of isoniazid may increase the risk of acetaminophen toxicity.152-154 Reported changes have been generally of limited clinical significance. Isoniazid Some reports suggest that patients on chronic isoniazid therapy may be at risk for developing hepatotoxicity from an acetaminophen overdose at doses that would not have been expected to produce toxicity. or taken regularly. The clinical significance of these findings has not been established. In two studies of induction. Diflunisal Professional literature from the manufacturer of diflunisal cautions that concomitant administration with acetaminophen produces an approximate 50% increase in plasma levels of acetaminophen in normal volunteers.148 and based on acetylation genotype.149-151 In other studies. prothrombin time did not change. it is important to monitor patient response to anticoagulation therapy with additional prothrombin time or INR determinations. including diet.142 Acetaminophen had no effect on diflunisal plasma levels. it also appears that isoniazid acetylation genotype may play a role in the activity of CYP2E1. no special dosage adjustment is generally required.142 There have been several reports that suggest that acetaminophen may produce hypoprothrombinemia (elevated international normalized ratio [INR] or prothrombin time) when administered with coumarin derivatives.biz Website :: http://icpc.143-145 Since patients on isoniazid therapy may develop hepatic effects from isoniazid alone. may affect how a patient responds to anticoagulant therapy.biz/PharmaceuticalDossier. However. medications. Volunteer studies demonstrate that isoniazid inhibits the formation of the toxic metabolite of acetaminophen when taken concurrently.142 54 Contact :: info@icpc.141 It is not known whether there is increased risk from an acetaminophen overdose in patients on chronic carbamazepine therapy. and environmental and physical states.XYZ PHARMACEUTICAL Carbamazepine At usual oral therapeutic doses of acetaminophen and carbamazepine.

82-85 In one study. gastric erosions.0 and 0. However. respectively.92. Acetaminophen is recommended as the analgesic/antipyretic of choice in aspirin/NSAID-sensitive patients. occult or overt gastrointestinal blood loss. the reactions to acetaminophen were generally mild and easily reversed.aspx .biz/PharmaceuticalDossier. randomized.90-92 a case-controlled study evaluating first-time peptic ulcer patients found no significant risk associated with acetaminophen use prior to gastric ulcer occurrence.biz Website :: http://icpc. a proportion had evidence of decreased pulmonary forced expiratory volume at 1 second (FEV1). And Special Precautions a. crossover.33 In an overdose situation. or is experiencing central nervous system effects secondary to fulminant hepatic failure. Gastrointestinal Effects In recommended therapeutic doses. this was not the case with acetaminophen. Coma or other evidence of central nervous system depression usually is not present unless the patient has taken a massive overdose. in contrast to the aspirin reactions. Safety Central Nervous System Effects Acetaminophen at recommended doses has no obvious effects on central nervous system function. 1000 mg of aspirin evoked a lesion score of 2.93 An American College of Gastroenterology survey found that OTC aspirin and NSAIDs were used significantly more often by patients in the gastrointestinal bleeding population than in controls. Toxicology.94 55 Contact :: info@icpc.86 No reactions were seen with acetaminophen at doses of 650 mg or less. when asthmatic patients who were sensitive to very low doses of aspirin were challenged with doses of 1000 to 1500 mg of acetaminophen. endoscopy study in 12 healthy volunteers. double-blind. central nervous system effects are uncommon. but. whereas 1000 mg of acetaminophen and placebo resulted in scores of 1. whereas acetaminophen is not associated with a risk for gastrointestinal bleeding. PRECAUTIONS Safety Perspectives. acetaminophen does not cause gastric irritation. or ulcers.87. Cross-Reactivity of Acetaminophen With Aspirin and NSAIDs Most studies do not show any cross-reactivity with the use of acetaminophen in aspirinsensitive patients.89 Several case-controlled studies have established that gastrointestinal bleeding is a significant risk with both regular and occasional aspirin or NSAID use. has taken other central nervous system-active agents concomitantly. whereas this was not the case with aspirin.88 In a placebo-controlled.5 (possible scores ranged from 0 [no mucosal lesions] to 3 [more than 10 petechiae or free blood in the lumen]).XYZ PHARMACEUTICAL WARNINGS Included as part of the PRECAUTIONS section.

controlled trials have demonstrated the safety of acetaminophen with chronic use. acetaminophen when taken in therapeutic doses of up to 4000 mg/d demonstrated no adverse hepatic effects. no causality was established. Although some authors suggest that alcoholics may be at increased risk from therapeutic doses. Acetaminophen in massive overdosage may cause hepatotoxicity in some patients.biz Website :: http://icpc. a single 1000-mg dose of acetaminophen was given to normal volunteers and did not affect bleeding time or platelet aggregation. as measured by bleeding time. randomized. toxicity associated with acetaminophen is almost invariably caused by ingestion of quantities of the drug that are significantly above the recommended dosage range. In adults and adolescents. no change in bleeding time or platelet aggregation was observed. no clinically important hepatic events occurred in aceta-minophen-treated patients. multicenter study established that acetaminophen is not associated with agranulocytosis or aplastic anemia. In one study.107 Chronic heavy alcohol abusers may be at increased risk of liver toxicity from excessive acetaminophen use. In both of these studies.000 febrile children in a randomized. acetaminophen may be preferred because it does not have any immediate or delayed effects on small-vessel hemostasis. hepatotoxicity may occur following ingestion of greater than 7. primarily letters to the editor. Lesko and Mitchell106 enrolled more than 84.102 In another study. In normal volunteers receiving a single dose of acetaminophen (975 or 1950 mg) or multiple doses of acetaminophen (1950 mg daily for 6 weeks). Two double-blind. In both adults and children. Bradley and colleagues49 compared acetaminophen (4000 mg/d) with analgesic (1200 mg/d) and antiinflammatory (2400 mg/d) doses of ibuprofen for 4 weeks. Williams and associates50 evaluated the relative safety and efficacy of acetaminophen (2600 mg/d) compared with naproxen (750 mg/d) for up to 2 years. fulminant hepatic failure.95 Although there have been infrequent reports. In children.5 to 10 g (ie. Of the children included in the analysis. Hepatotoxicity. amounts less than 150 mg/kg are highly unlikely to produce hepatotoxicity.104. In a large clinical study. Fatalities are infrequent (less than 3% to 4% of untreated cases) and have rarely been reported with overdoses less than 15 g (ie. doubleblind. in which thrombocytopenia was noted in patients receiving acetaminophen.130 received acetaminophen and none experienced serious adverse hepatic effects.XYZ PHARMACEUTICAL Hematologic Effects A case-controlled.105 Hepatic Effects In clinical studies in adults.96-101 Hemostatic Effects In various clinical conditions. 103 Patients with hemophilia receiving multiple doses of acetaminophen showed no significant changes in bleeding time.biz/PharmaceuticalDossier. ranging from transient sharp transaminase elevations to fatal. 45 regular-strength or 30 extra-strength caplets or tablets). 28. In the second study. 24 regular-strength or 15 extra-strength caplets or tablets) over a period of 8 hours or less.aspx . acetaminophen-controlled trial to assess the risks of rare but serious adverse events following use of pediatric ibuprofen. is the most common result of clinically significant overdosage. although reports of this event are rare. reports usually involve cases 56 Contact :: info@icpc.

Hypersensitivity and Allergy Allergic reactions (primarily skin rash) or reports of hypersensitivity secondary to acetaminophen are rare and generally are controlled by discontinuation of the drug and. Acetaminophen has been used for over 40 years and available data indicate that acetaminophen in therapeutic doses does not adversely affect the pregnant mother or the fetus. Accordingly.117 57 Contact :: info@icpc.biz/PharmaceuticalDossier. instructs consumers who are pregnant or nursing a baby to contact their doctor before use. and the majority had a history of the abuse of alcohol. the nursing infant would receive less than 2% of the maternal dose.24 In the fetus. acetaminophen is effectively metabolized by sulfate conjugation.116 Review of this case series revealed that all patients reported taking overdoses of acetaminophen.111-115 A report has suggested that hepatotoxicity following greater than the recommended dose of acetaminophen may be enhanced by both fasting and/or chronic alcohol ingestion.1% to 1.XYZ PHARMACEUTICAL of severe chronic alcoholics and the dosages of acetaminophen most often exceed recommended doses and often involve substantial overdose. Overdose One study that evaluated the subsequent outcome of pregnancy in women who had taken an acetaminophen overdose during the period from 1984 to 1992 demonstrated no increased risk for fetal malformation.biz Website :: http://icpc. acetaminophen crosses the placenta into fetal circulation as early as 30 minutes after ingestion. although the difference in serum concentration between maternal and cord blood is not statistically significant. symptomatic treatment.23 When given to the mother in therapeutic doses. Amounts in milk range from 0.108-110 Studies evaluating the metabolism of doses up to 20 mg/kg of acetaminophen in chronic alcohol abusers and a study evaluating the effects of 2 days of acetaminophen dosing at 4000 mg daily in chronic alcoholics undergoing detoxification do not support an increased risk of hepatotoxicity with recommended doses of acetaminophen. breast feeding need not be interrupted because of maternal medication with recommended doses of acetaminophen. Acetaminophen overdose alone is not an indication for termination of pregnancy. Pregnancy/Teratogenicity Acetaminophen labeling. when necessary.25 Nursing Maternal ingestion of acetaminophen in recommended analgesic doses does not present a risk to the nursing infant. like all OTC medications.aspx . Transplacental Passage Analysis of urine samples has demonstrated the passage of unconjugated acetaminophen via placental transfer. most had reported prolonged periods of fasting. even at the time of peak acetaminophen concentration in human breast milk.85% of the ingested maternal dose.26-28 These studies have established that.

Use in Certain Disease States or Conditions Glucose-6-Phosphate Dehydrogenase (G6PD) Deficiency In therapeutic doses. There were no abnormalities indicative of an adverse reaction to acetaminophen.119. are conflicting.121-125 A National Kidney Foundation position paper notes that there is negligible clinical evidence to suggest that the habitual use of acetaminophen causes analgesic nephropathy.biz Website :: http://icpc. limited by recall bias and confounded by the inability to determine whether analgesic use preceded or followed the onset of renal disease.biz/PharmaceuticalDossier.126 However. analgesics that contain aspirin and acetaminophen combined with caffeine or codeine) in large doses for prolonged periods of time is thought to be associated with an increased risk of renal papillary necrosis resulting in analgesic nephropathy. There were no significant differences in overall 24-hour urinary excretion of acetaminophen and glucuronide. acetaminophen does not shorten the lifespan of red blood cells127. crossover study that evaluated the use of 4000 mg/d of acetaminophen for 13 days in patients with stable chronic liver disease.aspx . Edwards and associates119 measured renal function in patients taking at least 1000 mg of acetaminophen daily for at least 1 year. Forrest and associates132 compared acetaminophen metabolism following a single 1500-mg dose in normal subjects. Acute nephrotoxicity has been reported following massive overdose either as a sequela of hepatic failure or. and patients with severe liver disease.120 Some studies suggest an association between the chronic long-term use of acetaminophen and renal effects. two-period. in the absence of hepatic failure.126 The panel concludes that acetaminophen has been preferentially recommended by physicians to patients with renal failure and that there is no evidence that occasional use of acetaminophen causes renal injury.129 Use in Chronic Liver Disease Acetaminophen can be used in patients with liver disease130 and has been studied in both onetime single (1500 mg) and multiple doses (4000 mg/d) in adult patients with chronic stable liver disease. acetaminophen was recommended as the non-narcotic analgesic of choice for episodic use in patients with underlying renal disease.33 In a single-blind study. Following a single (10 mg/kg) dose of acetaminophen. Acetaminophen did not have the adverse renal effects generally associated with NSAIDs. cysteine. In this position paper.131.132 Benson131 conducted a double-blind. occasionally. or severe liver disease were not 58 Contact :: info@icpc. sulfate. moderate. the pharmacokinetic profiles in pediatric patients with mild. b. use of antipyretic analgesic combinations (ie. Prescott and colleagues118 compared the effect of acetaminophen (4000 mg/d) with indomethacin (150 mg/d) and placebo on renal function in healthy volunteers. There was no evidence of clinically significant renal impairment in 18 patients who each consumed a cumulative total of 2 to 30 kg of acetaminophen over prolonged periods. and mercapturic acid conjugates of acetaminophen. patients with mild liver disease.XYZ PHARMACEUTICAL Renal Effects Clinical data have established that acetaminophen in recommended doses is not nephrotoxic.128 and does not produce any clinically perceptible destruction of circulating red blood cells. however. Results.

The fractional urinary recovery of acetaminophen and its conjugates (eg. The American Geriatrics Society Clinical Practice Guidelines for the Management of Chronic Pain in Older Persons136 recommend acetaminophen as the drug of choice for relieving mild to moderate musculoskeletal pain. A National Kidney Foundation position paper notes that physicians preferentially recommend acetaminophen to patients with renal failure because of the bleeding complications associated with aspirin in these individuals. In a 10-day. acetaminophen was recommended as the non-narcotic analgesic of choice for episodic use in patients with underlying renal disease.XYZ PHARMACEUTICAL significantly different. cysteine. mercapturic acid).aspx .126 In this position paper. The International Agency for Research on Cancer (IARC) found only limited evidence in animals for carcinogenicity and the US National Toxicology Program (NTP) found no evidence for carcinogenicity in mice and male rats and only equivocal evidence for carcinogenicity in female rats. however. In a single-dose study. acetaminophen can be used in patients with chronic renal disease without dosage adjustment.biz/PharmaceuticalDossier. glucuronide. Use in Older Patients No adjustment in labeled dosage is necessary for older patients who require acetaminophen therapy. multidose study.161. but there was no evidence of accumulation of the glutathione-derived metabolites of acetaminophen (eg. with the maximum dosage not to exceed 4000 mg daily. Use in Renal Disease Based on available clinical data. Although mean daily predose plasma concentrations of sulfate and glucuronide conjugates were higher in patients with chronic renal disease. mercapturate). Martin and associates135 evaluated the disposition of acetaminophen 3000 mg daily in healthy volunteers compared with patients with chronic renal failure. glucuronide. A slight increase in predose trough acetaminophen levels was noted in patients with renal failure (3. sulfate. no reduction in recommended dosage is necessary.1 µg/mL). cysteine. Negative results have been demonstrated in rodent bioassays of acetaminophen. There is no significant risk of acetaminophen toxicity in patients with moderate to severe renal failure. these conjugates disappeared rapidly when acetaminophen was discontinued. Prescott and colleagues134 compared the disposition and metabolite kinetics of 1000 mg of acetaminophen in patients with renal disease and in healthy volunteers.1 µg/mL) compared with controls (1.133 Although the plasma half-life of acetaminophen was prolonged in patients with severe liver disease. there were no significant differences in the 24-hour (adult) and 36-hour (children) urinary excretion of acetaminophen or its conjugates (eg.biz Website :: http://icpc. mercapturate) was similar in healthy volunteers and in patients with moderate renal failure.163 59 Contact :: info@icpc. Carcinogenicity/Mutagenicity (Animal) Various animal bioassays on a weight-of-evidence basis have demonstrated no evidence of carcinogenic potential for acetaminophen. sulfate. cysteine. Those who require therapy for longer than 10 days should consult their physician for condition monitoring.162 The equivocal results were based on a few studies with serious methodological problems.

or placental weight.XYZ PHARMACEUTICAL Carcinogenicity (Human) Although it has been hypothesized that long-term use of analgesics may be associated with a slight increase in urinary tract tumors and renal cell cancer in man. causing false-positive results. the United States Food and Drug Administration (FDA) approved acetylcysteine (NAC) as an antidote for the treatment of acetaminophen overdose.biz Website :: http://icpc. For further detail.aspx .155 OVERDOSE Overdose Management In January 1985.164-166 A comprehensive and conclusive review. case-controlled studies have shown that it is not likely that acetaminophen use plays a major role in renal cell cancer. Approval of acetylcysteine for this purpose was based on a nationwide research program conducted by the Rocky Mountain Poison and Drug Center under the sponsorship of McNeil Consumer Healthcare. a number of populationbased.169 In another study. When acetaminophen was given from day 16 of pregnancy through a 3-week lactation period. acetaminophen does not cause laboratory test interferences. it may be advisable to contact the specific laboratory instrumentation manufacturer. there are certain methods with which the possibility of laboratory changes exists.167 This review concluded that genotoxic effects of acetaminophen are not reached at therapeutic dosage. However.170 Potential Laboratory Test Interferences Using the most current analytic systems. considered the genotoxic and carcinogenic properties of acetaminophen. but a decrease in body weight gain and survival rate was noted among offspring of drug-treated females. as described below: Blood Tests Acetaminophen at recommended doses does not appear to interfere with glucose analysis using currently marketed blood glucose meters. Reproductive and Teratogenic Effects (Animal) There was no effect on pregnancy or offspring when acetaminophen was given at dose levels of 600 mg/kg/d in the diet of male rats for 60 days prior to mating and to female rats from 14 days before mating to the end of pregnancy. acetaminophen 250 mg/kg/d did not affect fetal length or weight.biz/PharmaceuticalDossier. incidence of resorptions. accepted by the Committee for Proprietary Medicinal Products (CPMP) of the European Union. This research clearly demonstrated the efficacy of acetylcysteine. when used early 60 Contact :: info@icpc.168. An oral dose of 600 mg/kg/d produced no teratogenicity or embryotoxicity when given from days 6 through 15 of pregnancy. no deleterious effect was noted on pregnancy rate or on percent of live births. Urine Tests Acetaminophen in therapeutic doses may interfere with the determination of 5hydroxyindoleacetic acid (5HIAA). False determinations may be eliminated by avoiding acetaminophen ingestion several hours before and during the collection of the urine specimen.

at the Rocky Mountain Poison and Drug Center. b) Syrup of ipecac given to children during the prehospital phase may reduce subsequent plasma levels of acetaminophen. Please do not hesitate to call this number if you need individualized consultation on managing a patient with an acetaminophen overdose.* A number of steps in the management of such an overdose are important to achieve an optimal clinical outcome. This section outlines basic steps in managing acute acetaminophen overdose. Fatalities are infrequent (less than 3% to 4% of untreated cases) with overdoses less than 15 g (ie. however. and a nomogram are provided (Figures 3 and 4.5 to 10 g (ie.biz Website :: http://icpc. Flowchart: Stepwise Management of Acute Acetaminophen Overdose Assessment Adults or adolescents ( ≥ 12 years of age). (For management of acetaminophen overdose in young children. Acute Overdose Management Acute acetaminophen overdose is defined as an ingestion of a toxic amount of acetaminophen occurring within a period of 8 hours or less. McNeil Consumer Healthcare continues to sponsor a toll-free telephone number (1-800-5256115). Gastric Decontamination/Prevention of Absorption Gastric decontamination should be carried out according to standard treatment guidelines. 24 regular-strength or 15 extra-strength caplets or tablets) over a period of 8 hours or less. Any individual presenting with an unknown amount of acetaminophen ingested or with a questionable or unreliable history about the time of ingestion should have a plasma acetaminophen level drawn and be treated with acetylcysteine. there is no evidence that syrup of ipecac administered later than 60 minutes postingestion is useful. available 24 hours a day. 45 regular-strength or 30 extra-strength caplets or tablets). consistent with FDA-approved labeling of acetylcysteine.) Estimate as carefully as possible the quantity and dosage form (see also Special Considerations: Extended-Release Acetaminophen) of acetaminophen ingested and the time of ingestion.aspx . hepatic toxicity may occur following ingestion of greater than 7. see Special Populations. FIGURE 3. who may have ingested acetaminophen in a purposeful overdose. In adults and adolescents.XYZ PHARMACEUTICAL in the course of treatment. it is reasonable to administer activated charcoal for up to 4 hours post-ingestion. 61 Contact :: info@icpc. independent of the amount reported to have been ingested. in reducing morbidity and virtually eliminating mortality associated with even a massive acetaminophen overdose. especially in the case of a mixed drug overdose. a. Young Children. Although there are no data to support the efficacy of activated charcoal beyond 2 hours. A flowchart outlining a stepwise approach. respectively).biz/PharmaceuticalDossier. should be referred for evaluation and have a plasma acetaminophen level determined. a) Activated charcoal should be given during the immediate postingestion period. Administration of activated charcoal will not interfere with subsequent administration of oral acetylcysteine therapy.

If an assay for acetaminophen cannot be obtained. Therefore. if a patient presents soon after the overdose.aspx . then wait until 4 hours to draw blood. determined at least 4 hours following an overdose. If the initial plasma acetaminophen level. Only the initial acetaminophen level is used in making the decision to initiate or continue acetylcysteine treatment (see also Special Considerations: Extended-Release Acetaminophen). the earliest possible ingestion time should be assumed. Interpretation of Acetaminophen Assays Refer to the nomogram in Figure 4 on the following page to plot the initial plasma acetaminophen level. If less than 4 hours have elapsed postingestion. regardless of the quantity of acetaminophen reported to have been ingested. If there is any question about the time of ingestion. if already initiated. determined as early as possible but no sooner than 4 hours following an acute overdose. The following procedures are recommended: 62 Contact :: info@icpc. it is important to verify the time of ingestion as accurately as possible. In order to err on the safe side. Draw blood immediately for the acetaminophen plasma assay if 4 hours or more have elapsed postingestion. If the initial plasma acetaminophen level plots above the treatment line. then acetylcysteine treatment is recommended. Values above the Rumack-Matthew line connecting 200 µg/mL at 4 hours with 50 µg/mL at 12 hours are reported to be associated with a potentially increased risk of hepatotoxicity if the antidote is not administered. treatment with acetylcysteine may be withheld until acetaminophen assay results are available. can be discontinued. are essential in assessing the potential risk of hepatotoxicity. even if subsequent acetaminophen levels plot below the treatment line. provided that initiation of treatment is not delayed beyond 8 hours following the overdose ingestion. A complete course of acetylcysteine should be provided if the initial level is above the treatment line. above the treatment line on the treatment nomogram). immediately administer acetylcysteine orally or with a nasogastric tube if 8 hours or more have elapsed from the reported time of ingestion of an acetaminophen overdose.biz Website :: http://icpc.biz/PharmaceuticalDossier.XYZ PHARMACEUTICAL Determining the Need for an Antidote Acetaminophen Assay Plasma or serum acetaminophen levels. Plasma levels provide a basis for determining the need to initiate or continue with maintenance doses of acetylcysteine treatment. dosing with acetylcysteine should be initiated and continued for the full course of therapy. it is necessary to assume that the overdose is potentially toxic. Levels obtained before 4 hours cannot be plotted on the nomogram (Figure 4). using the earliest possible ingestion time if there is any question about the time of ingestion. If an assay cannot be obtained or if the acetaminophen level is clearly in the toxic range (ie. FIGURE 4. Do not await results of assays for acetaminophen level before initiating acetylcysteine. It is important to verify as closely as possible the timing of the ingestion. plots below the treatment line described above. Single Acute Acetaminophen Overdose Nomogram Administration of Antidote Based on clinical experience. the risk of hepatotoxicity is minimal and acetylcysteine treatment is not necessary and. In adults and adolescents. a treatment line has been established that is 25% below the Rumack-Matthew line.

140 mg/kg of body weight. some poison control centers recommend aggressive antiemetic therapy or intravenous administration of acetylcysteine. acetylcysteine may be continued beyond the full course of therapy until liver enzymes are decreasing and prothrombin time is returning to normal. (Some toxicology authorities have adopted shorter courses of therapy based on their own specific clinical parameters. the concern is that absorption of extended-release acetaminophen is slower than that of immediate-release acetaminophen. The intravenous dosage form of acetylcysteine is not approved for use in the United States. As a result. obtain aspartate aminotransferase (AST) or alanine aminotransferase (ALT) levels. In symptomatic patients or patients with increased plasma acetaminophen levels. referral to a transplant center may be necessary. repeat the dose. blood glucose. In rare cases.) c) If the patient vomits the loading dose or any maintenance dose within 1 hour of administration.biz/PharmaceuticalDossier. Repeat the AST (or ALT) level daily during therapy if the plasma acetaminophen level is in the potentially toxic range. If more than 8 hours have elapsed post-ingestion and the patient is persistently unable to retain orally administered acetylcysteine. Supportive Treatment a) Monitor for signs and symptoms of incipient hepatic failure and provide appropriate supportive care. 63 Contact :: info@icpc. prothrombin time or international normalized ratio (INR). creatinine. asymptomatic patients with early presentation.biz Website :: http://icpc. If liver enzymes continue to be elevated. then bilirubin. blood urea nitrogen (BUN). Special Considerations: Extended-Release Acetaminophen The extended-release form of acetaminophen is composed of one layer containing 325 mg of immediate-release acetaminophen and another layer containing 325 mg of extended-release acetaminophen.XYZ PHARMACEUTICAL a) Administer the oral loading dose of acetylcysteine. The oral maintenance dose is then repeated at 4-hour intervals for a total of 17 maintenance doses. If AST or ALT levels are abnormal. electrolyte. In cases of overdose. d) For patients who are persistently unable to retain orally administered acetylcysteine. blood glucose. electrolyte. Other Laboratory Tests Specific baseline laboratory tests are not necessary in otherwise healthy. obtain appropriate toxicology or hepatology consultation. especially in cases showing evidence of significant toxicity. administer the first of 17 oral maintenance doses. and pH levels may be useful. creatinine. but is recommended by some poison control centers in selected cases. Bilirubin. Consult a regional poison control center for these protocols or see page 23 for additional consultation sources. the plasma acetaminophen level may plot below the treatment line of the nomogram at 4 hours but may rise above the treatment line with continued absorption. b) In cases in which fulminant hepatic failure develops. you may want to consult a poison control center for protocols on the use of antiemetics or intravenous acetylcysteine. b) Four hours after the loading dose. 70 mg/kg of body weight. prothrombin time or INR.aspx . and pH levels also should be obtained. BUN.

biz/PharmaceuticalDossier. toxicity is unlikely and acetylcysteine treatment is not necessary and. In children. Serious toxicity or fatalities have been extremely infrequent following an acute acetaminophen overdose in young children. gastric emptying with syrup of ipecac or administration of activated charcoal should be considered.aspx . obtain a plasma acetaminophen level as soon as possible. who presented 36 to 80 hours postingestion. can be discontinued.biz Website :: http://icpc. b) If either of the levels plot above the treatment line of the nomogram. plasma acetaminophen concentrations should be measured at least 4 hours after ingestion. Pregnant Women Acetylcysteine should not be withheld from pregnant women who have ingested an acetaminophen overdose. If the plasma acetaminophen level can be obtained within 8 hours postingestion. caused by purposeful overdose of acetaminophen. patients with demonstrated hepatic toxicity may receive a full course of acetylcysteine. it may be prudent to obtain a second level. In patients referred for plasma acetaminophen levels. acetylcysteine treatment should be administered. Until there is further evidence. Evidence suggests that acetylcysteine treatment may improve survival in patients presenting late and may be appropriate almost any time after overdose ingestion. Because of differences in absorption rates. an acute overdosage of less than 150 mg/kg has not been associated with hepatic toxicity. whereas others do not. Contact a regional poison control center for guidance on managing patients presenting 24 hours or more postingestion (see Additional Consultation). However. if the estimated time postingestion is approaching 8 hours. Special Populations Young Children ( < 12 Years of Age) If more than 150 to 200 mg/kg or an unknown amount was ingested." Patients Presenting 24 Hours or More Postingestion Acetylcysteine may have a role in the management of patients who present more than 24 hours after an acetaminophen overdose. acetylcysteine treatment should be initiated and continued for a full course of therapy. if already initiated. A full course of acetylcysteine treatment should be administered using the same indications for treatment as described on page 20 in the section entitled "Determining the Need for an Antidote. initiating acetylcysteine treatment is not necessary until the result is obtained. Although the benefit of acetylcysteine in patients who present more than 24 hours postingestion but without established fulminant hepatic failure has not been confirmed. 64 Contact :: info@icpc. If the acetaminophen level plots above the treatment line on the nomogram.XYZ PHARMACEUTICAL a) After an acute overdose with an extended-release acetaminophen product. possibly because of differences in the way children metabolize acetaminophen. then acetylcysteine treatment should be initiated immediately. but not sooner than 4 hours following ingestion. A well-controlled study has indicated that intravenous acetylcysteine improves survival in patients with established fulminant hepatic failure. c) If both levels plot below the treatment line. Some authorities recommend obtaining a second plasma acetaminophen level 4 to 6 hours after the first measurement. the significance of delayed rising levels is not clear.

the use of the nomogram is not appropriate. Reports usually involve cases of severe chronic alcoholics. 1-800-525-6115. although reports of this event are rare. Acetylcysteine treatment should be considered in patients with a history of chronic overdose. In such a circumstance. Normally.* In these cases. the reactive intermediate metabolite binds to hepatic cell macromolecules. It is estimated that when the amount of available glutathione is reduced to approximately 30% of normal. Thus.aspx .biz/PharmaceuticalDossier. In these cases. toxicity does not occur. acetaminophen sulfate. at the Rocky Mountain Poison and Drug Center. nor the glutathionederived metabolites are toxic. The reactive intermediate metabolite formed through the P450 pathway conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates. Neither acetaminophen glucuronide. the amount of glutathione available in the liver may become insufficient to conjugate with and detoxify the reactive intermediate metabolite. For additional individualized consultation. The exact mechanism of hepatocellular damage 65 Contact :: info@icpc. McNeil Consumer Healthcare sponsors a toll-free telephone number. following a substantial overdose. In young children. consult your regional poison control center or the Rocky Mountain Poison and Drug Center (see Additional Consultation).biz Website :: http://icpc. The likelihood of increased risk of hepatotoxicity in chronic alcohol users following an acute acetaminophen overdose is unresolved.XYZ PHARMACEUTICAL Chronic Alcohol Users Chronic heavy alcohol users may be at an increased risk of hepatic toxicity from excessive acetaminophen use. available 24 hours a day. the amount of reactive intermediate metabolite produced may increase markedly. However. Clinical Characteristics of Acute Acetaminophen Overdose The principal toxic effect of a substantial acetaminophen overdose is hepatic injury. and (c) metabolism via the cyto-chrome P450dependent mixed function oxidative enzyme pathway to form a reactive intermediate metabolite. For further assistance. (b) conjugation with sulfate (sulfation). producing cellular necrosis. a full course of acetylcysteine treatment should be administered using the same indications for treatment as described on page 20 in the section entitled "Determining the Need for an Antidote. Additional Consultation Consult your regional poison control center for additional emergency information or treatment recommendations. with normal therapeutic use. especially when signs and symptoms are consistent with acetaminophen toxicity. acetaminophen metabolism involves three separate pathways: (a) conjugation with glucuronide (glucuronidation). and the dosages of acetaminophen most often exceed recommended doses and often involve substantial overdose. daily doses of more than 150 mg/kg/24 h or more for several days have been reported to result in hepatic toxicity. Hepatotoxicity has been documented in some patients who have reported ingesting repeated overdoses (greater than the maximum daily recommended dose of 4 g/24 h) of acetaminophen." Chronic (Repeated) Overdose Chronic overdose is defined as an ingestion of toxic amounts of acetaminophen taken for a period longer than 8 hours.

obtain a plasma acetaminophen level and initiate antidotal therapy. spontaneous vomiting following a substantial overdose occurs frequently and may play a role in the reduced risk of toxicity in children. serial liver biopsies and liver function tests have shown prompt resolution with no significant residual functional or architectural alterations of the liver. The patient may manifest signs of gastrointestinal irritability. Signs and symptoms of this third phase of the clinical course depend on the severity of hepatic damage and usually occur from 3 to 5 days following ingestion. it may be overlooked. with hepatic enzymes often rising to striking levels. In small children.aspx . The clinical course of acetaminophen overdose generally occurs in a three-phase sequential pattern: Phase I The first phase begins shortly after ingestion of a potentially toxic overdose and lasts for 12 to 24 hours. Acetaminophen Overdose: Summary Acetaminophen overdose can be effectively managed by focusing on a few basic principles. coagulation defects. Many patients with early symptoms never progress beyond the first phase and recover without additional problems. and pallor. and sequelae of hepatic necrosis including jaundice. this may proceed to hepatic failure. The subsequent clinical course is characterized by a gradual return of liver function tests to normal. hypoglycemia.XYZ PHARMACEUTICAL is not known. and prothrombin time or INR values will progressively rise. hepatic enzymes. With increasing hepatocellular necrosis. In severe cases. stupor. and encephalopathy. As in all cases of poisoning. especially if given acetylcysteine treatment. general malaise. Most patients do not progress beyond this phase. Initial symptoms abate and the patient may feel better. However. Coma or other evidence of central nervous system depression is usually not present unless the patient has taken a massive overdose or has also ingested toxic doses of barbiturates.biz/PharmaceuticalDossier. Right upper-quadrant pain may develop as the liver becomes enlarged and tender. if it occurs. nausea. Symptoms may be limited to anorexia. Mortality rates in patients with toxic plasma levels who do not receive antidotal therapy are in the range of 3% to 4%. there is a latent phase of up to 48 hours. as may be the case in suicide attempts. hepatic dysfunction occurs. diaphoresis. morbidity is significantly reduced and mortality virtually eliminated. tranquilizers. vomiting. show a consistent pattern but are not diagnostic or predictive of risk. is generally a result of complications associated with fulminant hepatic failure. Signs and symptoms of acetaminophen overdose. Phase II If toxicity continues or is to ensue. but is reflected by a rise in serum transaminases. Death. during the initial management phase. or other central nervous system depressants. However. The larger the overdose. and abdominal pain in less severe cases or may progress to confusion. and unless the possibility of acetaminophen overdose is considered during this early phase. Phase III A few patients will develop serious hepatic necrosis. obtain a careful history and have a high index of suspicion. When the antidote. The 66 Contact :: info@icpc. these symptoms are not unique to acetaminophen. acetylcysteine. anorexia. is administered using current recommendations. In nonfatal cases. When acetaminophen overdose is a possibility.biz Website :: http://icpc. bilirubin. as well as renal failure and cardiomyopathy. nausea. the more likely that these symptoms are present.

Pharmacologic Class Acetaminophen is a centrally acting analgesic and antipyretic agent.aspx . for the pain of menstrual cramps.12 This has been demonstrated in animals by observing a decrease in both fever and PGE activity following administration of acetaminophen to unanesthetized cats. for the minor pain of arthritis.11. Mechanism of Action Analgesia Although the exact site and mechanism of analgesic action is not clearly defined. and adults. provided treatment is given expeditiously and appropriately.14 d. CONTRAINDICATIONS No information provided. muscular aches.2-4 The potential mechanism may involve inhibition of the nitric oxide pathway mediated by a variety of neurotransmitter receptors including N-methyl-D-aspartate and substance P. b. and for the reduction of fever. headache. Pharmacokinetic Data Absorption Regular-Release 67 Contact :: info@icpc.biz/PharmaceuticalDossier.5 Antipyresis Investigations indicate that endogenous pyrogens produced by leukocytes cause an elevation of prostaglandin E (PGE) in the cerebrospinal fluid.10 Acetaminophen does not depend upon the activation of the arginine vasopressin V-1 receptor to induce antipyresis as has been noted in rats treated with indomethacin and salicylates. toothache.biz Website :: http://icpc.13.6-9 Inhibition of arachidonic acid metabolism is not requisite for the antipyretic effect of acetaminophen. CLINICAL PHARMACOLOGY Pharmacologic Classification a. Fever results when the elevated PGE acts on the preoptic area of the anterior hypothalamus to decrease heat loss and increase heat gain. Acetaminophen has been shown to inhibit the action of endogenous pyrogens on the heatregulating centers in the brain by blocking the formation and release of prostaglandins in the central nervous system.XYZ PHARMACEUTICAL prognosis for patients with acetaminophen overdose is excellent. c. backache. and in rabbits and dogs when brain prostaglandin synthetase was inhibited by the administration of acetaminophen. General Acetaminophen is an analgesic and antipyretic agent and has been clinically proven to be effective for the temporary relief of minor aches and pains associated with the common cold. Acetaminophen is an effective antipyretic in infants. children. acetaminophen appears to produce analgesia by elevation of the pain threshold.

For individual subjects.15 Figure 1 shows the mean pharmacokinetic profile for 24 fasting subjects who received acetaminophen 1000 mg dosed as liquid or caplets. Acetaminophen plasma concentrations range from 1 to 4 µg/mL 6 hours after ingestion.biz Website :: http://icpc.aspx . 68 Contact :: info@icpc. Extended-Release Each bilayered acetaminophen extended-release. Mean plasma concentrations of acetaminophen in 24 male subjects following oral administration of 1300 mg acetaminophen dosed as either two caplets of TYLENOL® Arthritis Extended Relief or four Regular Strength TYLENOL® acetaminophen (two caplets given at 0 and 4 hours). 650-mg caplet contains 325 mg of immediate-release acetaminophen on one side and. 325 mg of acetaminophen in a matrix formulation designed to slowly release.biz/PharmaceuticalDossier.XYZ PHARMACEUTICAL Oral acetaminophen is rapidly and almost completely absorbed from the gastrointestinal tract primarily in the small intestine. maximal plasma concentrations occurred within 10 to 90 minutes following ingestion and ranged from 8 to 32 µg/mL. In vitro data indicate that two 650-mg extended-release caplets FIGURE 1. on the other side. The relative bioavailability ranges from 85% to 98%. Mean plasma concentrations of acetaminophen in 24 male subjects following oral administration of 1000 mg of acetaminophen dosed as either 30 mL of Extra Strength TYLENOL® acetaminophen Adult Liquid Pain Reliever or as two Extra Strength TYLENOL® acetaminophen Caplets. FIGURE 2. This absorption process occurs by passive transport.

19 The sulfate and glucuronide metabolites do not bind to plasma proteins even at relatively high concentrations. respectively.XYZ PHARMACEUTICAL (containing a total of 1300 mg of acetaminophen) release 88% and 95% of the drug within 3 and 5 hours.95 L/kg. Distribution Acetaminophen appears to be widely distributed throughout most body fluids except fat.24 In the fetus. acetaminophen crosses the placenta into fetal circulation as early as 30 minutes after ingestion. Figure 2 shows the mean pharmacokinetic profile for 24 fasting subjects who received acetaminophen 1300 mg dosed as two extended-release or four regular-strength caplets (two caplets given at 0 and 4 hours). the average maximal plasma concentrations occurred within 0.23 When given to the mother in therapeutic doses.25 69 Contact :: info@icpc.biz Website :: http://icpc. extended-release caplets.biz/PharmaceuticalDossier.21.1 µg/mL.16 Following administration of a single dose of two 650-mg.17 A relatively small proportion (10% to 25%) of acetaminophen is bound to plasma proteins and binding is only slightly increased in plasma concentrations associated with overdose.18.20 Spinal Fluid Low protein binding and low molecular weight allow acetaminophen to pass through the blood-brain barrier.aspx . The peak concentration of acetaminophen in cerebrospinal fluid is reached after 2 to 3 hours.9 to 14. although the difference in serum concentration between maternal and cord blood is not statistically significant. The apparent volume of distribution of acetaminophen is 0.5 to 3 hours following ingestion and ranged from 6.22 Placental Barrier Analysis of urine samples has demonstrated the passage of unconjugated acetaminophen via placental transfer. acetaminophen is effectively metabolized by sulfate conjugation.

34 Excretion The biologic half-life of acetaminophen in normal adults is approximately 2 to 3 hours in the usual dosage range.30-32 Two additional minor pathways also are possibly involved in acetaminophen metabolism:33 a) hydroxylation to form 3-hydroxy-acetaminophen b) methoxylation to form 3-methoxy-acetaminophen.85% of the ingested maternal dose. These metabolites are further conjugated with glucuronide or sulfate. breast feeding need not be interrupted because of maternal ingestion of recommended doses of acetaminophen. mixed-function oxidative enzyme pathway to form a reactive intermediate metabolite.21 Acetaminophen is eliminated from the body primarily by formation of glucuronide and sulfate conjugates in a dose-dependent manner. which conjugates with glutathione and is then further metabolized to form cysteine and mercapturic acid conjugates. The elimination half-life of acetaminophen in the cerebrospinal fluid according to pooled data is 3. the majority of acetaminophen is conjugated with glucuronic acid and. the sulfate conjugate predominates. Amounts in milk range from 0. with CYP1A2 and CYP3A4 as additional pathways. to a lesser extent.26-28 These studies have established that. Metabolism Acetaminophen is primarily metabolized in the liver by first-order kinetics and involves three principal separate pathways: a) conjugation with glucuronide b) conjugation with sulfate c) oxidation via the cytochrome.biz Website :: http://icpc.8 In premature infants.aspx .XYZ PHARMACEUTICAL Breast Milk Maternal ingestion of acetaminophen in recommended analgesic doses does not present a risk to the nursing infant. Table 1 0n the following page shows the mean range of acetaminophen urinary metabolite values in healthy subjects using therapeutic doses (10 70 Contact :: info@icpc.1% to 1. Accordingly. sulfate-. P450-dependent. even at the time of peak acetaminophen concentration in human breast milk.35 It is somewhat shorter in children and somewhat longer in neonates and in patients with cirrhosis.18 The elimination half-life is approximately 3 hours for the extended-release product. and glutathione-derived metabolites lack biologic activity. with sulfate. These glucuronide-.23.2 hours.biz/PharmaceuticalDossier. In adults.29 The principal cytochrome P450 isoenzyme involved appears to be CYP2E1. newborns.21. the nursing infant would receive less than 2% of the maternal dose. and young infants.

d Every 4 to 6 hd.9 2.8 mL Children's TYLENOL Elixir 160 mg/5 mL Children's TYLENOL Suspension Liquid 160 mg/5 mL Children's TYLENOL Chewable Tablets 80 mg Junior Strength TYLENOL Chewable Tablets 160 mg Junior Strength TYLENOL Caplets 160 mg a Dosing to be based on age or weight (approximately 10-15 mg/kg/dose.39.37 TABLE 1.36-40 Less than 9% of acetaminophen is excreted unchanged in the urine. Pediatric TYLENOL® acetaminophen preparations Strengtha Preparation Infants'TYLENOL Concentrated Drops 80 mg/0.0 3. and 3methyl-thioacetaminophen.8. Asian.35.44-46 71 Contact :: info@icpc.8 .e Every 8 hd. e Not to exceed 8 tablespoons per day. Spanish).1 .3. each accounting for 4% or less of a therapeutic dose.62.4 .aspx .0 2. c Not to exceed 8 tablets per day d Not for use in children under 12 years of age. Other minor metabolites.4 .biz Website :: http://icpc.biz/PharmaceuticalDossier. b Not to exceed 12 tablets per day. f Not to exceed 6 caplets per day. include sulfate and glucuronide conjugates of 3-methoxy-acetaminophen.36.XYZ PHARMACEUTICAL mg/kg or 1000-mg dose). Acetaminophen metabolites found in urine Acetaminophen metabolite Glucuronide Sulfate Mercapturate Cysteine conjugate Free acetaminophen Range of mean percent 46. TABLE 3.f Preparation Regular Strength TYLENOL Tablets/Caplets Extra Strength TYLENOL Tablets/Caplets/Gelcaps/Geltabs Adult Liquid Strength 325 mg 500 mg 500 mg/15 mL 1000 mg 1000 mg 1300 mg TYLENOL Arthritis Extended Relief 650 mg Caplets a Not to exceed 4000 mg in any 24-hour period.7 .7 TABLE 2. not to exceed 5 doses in 24 hours). 3-hydroxy-acetaminophen.5.41-43 Slight differences have been seen in ethnically distinct populations (eg. Adult TYLENOL® acetaminophen preparations Adult single Frequencya dose 650 mg Every 4 to 6 hb Every 4 to 6 hc.2 25.

64 Headache Three randomized. double-blind. b.58 Comparative clinical studies of the antipyretic efficacy of acetaminophen and ibuprofen administered in recommended dosages to pediatric patients suggest that both drugs are effective.63 In these studies.56.48-50 In a doubleblind. published in 1995. Clinical research has substantiated efficacy in pain associated with the following conditions: Arthritis Pain At recommended dosages. Acetaminophen taken for 1 month to 2 years is beneficial in relieving osteoarthritic pain and causes no significant adverse effects. Analgesia Clinical Studies: Therapeutic Comparisons With Other Drugs Or Treatments a. In a randomized. Williams and associates50 noted that acetaminophen was similar to naproxen in improving pain on motion and in physicians' global assessment of disease activity.60 Acetaminophen 10 mg/kg or 12.XYZ PHARMACEUTICAL In controlled trials. single-dose.59-62 However.61.53-56 Tepid sponging and acetaminophen have been shown to be approximately equivalent for the initial 30 minutes of treatment. multicenter. Bradley and colleagues49 reported that acetaminophen was comparable to both doses of ibuprofen in relieving pain. The combination of acetaminophen and sponging may provide additive benefit.aspx . ibuprofen. Amadio and Cummings48 found that 1000 mg of acetaminophen administered four times daily was significantly more effective than placebo in relieving tenderness. pain at rest.52. and naproxen in patients with osteoarthritis of the knee. 51.62 Acetaminophen 12. placebo-controlled study.54.biz Website :: http://icpc.5 mg/kg or 10 mg/kg. and pain on motion. There is no significant difference in antipyresis between equivalent doses of aspirin and acetaminophen.biz/PharmaceuticalDossier. In a double-blind study lasting up to 2 years that compared the relative safety and efficacy of acetaminophen (2600 mg/d) to naproxen (750 mg/d).59. Acetaminophen at a dose of 15 mg/kg is equivalent to ibuprofen at a dose of 10 mg/kg. Studies have been performed in a variety of pain models to assess the overall efficacy of acetaminophen. Clinical studies have compared the efficacy of acetaminophen to placebo. acetaminophen is well tolerated and effective for the treatment of minor pain of arthritis. American College of Rheumatology* Guidelines for the Medical Management of Osteoarthritis.5 mg/kg does not produce the same degree of antipyresis as ibuprofen 7. recommend acetaminophen in doses up to 4000 mg daily as the preferred first-line therapy in patients with symptomatic osteoarthritis of the knee.5 mg/kg is superior to ibuprofen 5 mg/kg. results vary depending on the dosage of each agent administered. double-blind study comparing acetaminophen (4000 mg/d) with analgesic (1200 mg/d) and anti-inflammatory (2400 mg/d) doses of ibuprofen. placebo-controlled studies have been conducted by McNeil (unpublished). which evaluated the efficacy of acetaminophen in 72 Contact :: info@icpc. but at the expense of additional discomfort to the child. onset of antipyresis with acetaminophen generally occurred within 30 to 60 minutes following administration and peak antipyresis was noted at 2 to 3 hours. acetaminophen was shown to be superior to placebo. after which acetaminophen is superior. Antipyresis Acetaminophen is effective in the treatment of various disorders associated with pain of mild to moderate intensity.57.

but in some studies ibuprofen 400 mg provided greater pain relief than acetaminophen 1000 mg in patients with moderate to severe baseline pain. single-dose studies (unpublished) evaluated patients who had undergone oral surgery and were experiencing moderate to severe pain. Most studies showed that both active treatments were effective compared with placebo. Acetaminophen and naproxen were rated significantly higher than placebo but were not different from each other.68 In another study. patients were treated with acetaminophen 1000 mg. patients were randomized to receive 500 mg of diflunisal or 1000 mg of acetaminophen prior to oral surgery.aspx . or placebo.67. aspirin.66 Three studies (unpublished) compared the relative analgesic efficacy of acetaminophen. Both treatments were effective and the difference in mean overall pain scores between the two regimens was not significantly different. naproxen sodium 220 mg and 440 mg.65. Post-Oral Surgery Pain Several dose-ranging studies have assessed the efficacy of acetaminophen in post-oral surgery pain. Two randomized. however. Two double-blind. naproxen sodium 440 mg.69 Quiding and colleagues70 evaluated the analgesic efficacy of a two-dose regimen of codeine 60 mg compared with acetaminophen 1000 mg in patients undergoing surgical removal of a third molar tooth. and placebo. In two randomized studies. Acetaminophen 500 mg was used as the control. In the first study. The active treatments were more effective than placebo. In these studies. naproxen 375 mg. acetaminophen 1000 mg was superior to acetaminophen 650 mg. The third study evaluated acetaminophen 1000 mg.biz/PharmaceuticalDossier. ibuprofen 200 mg. Both active treatments were significantly better than placebo. Naproxen sodium was significantly more effective than acetaminophen for patients with baseline pain of moderate severity. The second study compared the efficacy of acetaminophen 1000 mg. and the efficacy of codeine 60 mg corresponded approximately to acetaminophen 500 mg. double-blind studies (unpublished) evaluated the onset of analgesia using acetaminophen 1000 mg.XYZ PHARMACEUTICAL the tension headache model. After two doses. acetaminophen 1000 mg and aspirin 1000 mg were significantly more effective than placebo but were not different from each other. Several studies have compared the analgesic efficacy of acetaminophen and ibuprofen following dental surgery. Two doubleblind. acetaminophen 2000 mg did not provide greater analgesia compared with acetaminophen 1000 mg. and placebo in patients who 73 Contact :: info@icpc. For more severe pain. comparisons of patients with severe baseline pain were not significantly different between the active treatment groups. and neither strength of ibuprofen was different from acetaminophen. ibuprofen 400 mg. However.biz Website :: http://icpc. and placebo. and placebo in patients experiencing pain following dental surgery. ibuprofen 400 mg was significantly more effective than ibuprofen 200 mg in patients' overall evaluation. In a third study. acetaminophen 650 mg and 1000 mg was superior to placebo in all summary measures for moderate pain. single-dose studies demonstrated that acetaminophen 975 mg and 1000 mg were significantly better than aspirin 650 mg in relieving pain. acetaminophen 1000 mg was superior to acetaminophen 500 mg.

acetaminophen 650 mg. The first study found that all active treatments were more effective than placebo. ketorolac 10 mg. or placebo. and no difference for onset of pain relief between the active treatments was observed. In terms of analgesic efficacy.71 Kantor and associates72 compared the effects of single doses of acetaminophen 600 mg and aspirin 600 mg or 1200 mg in postpartum patients. and 12 hours 74 Contact :: info@icpc. bromfenac. bromfenac 10 mg was similar to acetaminophen 1000 mg.75 In the second study. and 4. ibuprofen 200 mg. propoxyphene/acetamino-phen combination.XYZ PHARMACEUTICAL experienced moderate to severe postoperative dental pain. and placebo. The three active treatments were significantly superior to placebo. and placebo were evaluated in a randomized. 8. patients were randomized to receive placebo.73 The analgesic efficacies of acetaminophen 650 mg. and both were superior to placebo. Orthopedic Surgery McQuay and colleagues74. The two active drugs were comparable in the treatment of primary symptoms of dysmenorrhea. acetaminophen 1000 mg. propoxyphene. bromfenac 5 mg.75 performed two studies comparing the analgesic equivalence and efficacy of varying doses of ketorolac.aspx . or ketorolac 20 mg. Capsules were taken at the time of the vaccination. bromfenac 10 mg. In the first study. The second study demonstrated that all active treatments had shorter time to onset of pain relief and were more effective than placebo. In a double-blind evaluation comparing acetaminophen. ibuprofen 400 mg three times daily. Hospital personnel volunteers were randomly assigned to acetaminophen 325 mg. Post-Immunization Muscle Aches and Pain Aoki and associates76 evaluated the effect of acetaminophen on the incidence of adverse effects and immunogenicity of whole-virus influenza vaccine in healthcare workers.biz Website :: http://icpc. ketorolac 5 mg.74 Menstrual Pain/Dysmenorrhea A randomized crossover study (unpublished) in primary dysmenorrhea compared the effect of acetaminophen 1000 mg four times daily. Ketorolac 20 mg was superior to acetaminophen 500 mg and ketorolac 5 mg and 10 mg but was not superior to acetaminophen 1000 mg. Both active treatments were superior to placebo. Acetaminophen 1000 mg was significantly superior to acetaminophen 500 mg. and placebo in patients with a history of recurrent moderate to severe dysmenorrhea. acetaminophen 1000 mg. double-blind study (unpublished) involving hospitalized postpartum patients with moderate to severe pain due to episiotomies. patients were treated with placebo plus one of the following: acetaminophen 500 mg. Episiotomy Pain Postpartum patients receiving a single 600-mg dose of acetaminophen reported a degree of relief greater than with either salicylamide or placebo and equivalent to the same dose of aspirin. acetaminophen alone was comparable to the propoxyphene combination and superior to both propoxyphene alone and placebo. whereas ibuprofen was significantly better than acetaminophen.biz/PharmaceuticalDossier. or bromfenac 25 mg. and acetaminophen in patients who had elective orthopedic surgery.

Moertel and colleagues78 compared acetaminophen 650 mg. and sore throat.79-81 Toxicology A number of acute. mortality rate. some renal tubular degeneration. heart. codeine 65 mg. 200 mg/kg/d. neither propoxyphene nor ethoheptazine was statistically superior to placebo. No drug-related changes were seen in mortality rate or necropsy findings compared with controls. histologic findings included areas of hepatic necrosis. or lungs. subacute. and gross necropsy observations were not significantly different from control values.157 Acetaminophen incorporated into the diet of rats for 100 days showed that the minimum dose that caused death in all rats was 1060 mg/kg/d. Acute Toxicity (Multiple Animal Models) See Table 5. aspirin 650 mg. slight renal tubular cell cloudy swelling was noted in three high-dose and one low-dose dog.XYZ PHARMACEUTICAL after vaccination. Slight thyroid hyperplasia was seen on histopathologic examinations in the six high-dose dogs.biz/PharmaceuticalDossier. three high-dose. Acetaminophen 650 mg significantly reduced the incidence of sore arm and nausea without affecting antibody response. kidney. and chronic toxicity studies in animals show that the toxic effects of acetaminophen appear only at extremely high doses. Subacute Toxicity (Rats) Oral doses of up to 1000 mg/kg/d or intramuscular doses of up to 100 mg/kg/d were given to rats for 13 days or 30 days. pentazocine 50 mg. propoxyphene 65 mg. and two low-dose animals. respectively. On the basis of mean pain relief scores.aspx . or histologic findings in liver. Sore Throat The analgesic efficacy of acetaminophen also has been demonstrated in pain associated with tonsillectomy. gross pathology.158 75 Contact :: info@icpc. Cancer Pain Wallenstein and Houde77 found 600 mg of acetaminophen or aspirin to be approximately equivalent and significantly superior to salicylamide and placebo for pain relief in patients with cancer. the dose that caused death in 50% of rats was 765 mg/kg/d. and pentazocine for pain relief. given to rats once a day by gavage for 28 weeks produced no changes in weight gain. tonsillitis. and ethoheptazine 75 mg in the treatment of cancer pain. and testicular atrophy. laboratory determinations.156 Chronic Toxicity (Rats) Acetaminophen.biz Website :: http://icpc. and slight liver glycogen depletion was found in one control. aspirin. Subacute Toxicity (Dogs) After acetaminophen (20 and 63 mg/kg/d) was given intramuscularly for 4 weeks to dogs. Acetaminophen was superior to placebo and comparable to codeine. At or near the LD50 (100 days). and the maximum dose that caused no deaths was 413 mg/kg/d.

Acute toxicity (LD50 mg/kg) of acetaminophen Species Rat (1 day old) Rat Mouse Hamster Rabbit Dog NT= not tested. with no evidence of interstitial nephritis or papillary necrosis. CONSUMER IMPORTANT NOTE: This is a summary and does not contain all possible information about this product.biz Website :: http://icpc. 50 to 400 mg/kg/d of acetaminophen for 13 to 40 weeks failed to produce any significant renal abnormalities. warrant. < 700 NT NT NT NT NT Renal tubular lesions were observed in rats given single doses of acetaminophen in the lethal range of 2000 to 7000 mg/kg.159 Renal lesions have occurred in rats given 300 mg/kg/d for periods of up to 32 weeks in the presence of experimentally induced renal infection. and similar lesions were found in rats given 500 to 4000 mg/kg daily for up to 100 days. and dogs.ORAL COMMON BRAND NAME(S): Panadol. effective.160 * The American College of Rheumatology is an independent professional. Acute Nephrotoxicity (Rats) Oral NT 2680-3100 NT 630-770 2640-2800 1180-1450 Intramuscular NT > 600 536-891 > 300. ask your health care professional. or appropriate for you. whereas the same dose of acetaminophen failed to cause renal lesions in rats without pyelonephritis. Always seek the advice of your health care professional if you have any questions about this product or your medical condition.aspx . Attempts to produce renal damage with single nonlethal doses of acetaminophen have been unsuccessful.XYZ PHARMACEUTICAL TABLE 5. and scientific society that does not guarantee. This information does not contain any assurances that this product is safe.159 Chronic Nephrotoxicity (Rats) In studies using rats. For complete information about this product or your specific health needs. ≤ 548 NT > 66 Subcutaneous > 600. or endorse any commercial product or service. ACETAMINOPHEN . rabbits. Tylenol USES: 76 Contact :: info@icpc. medical. This information is not intended as individual medical advice and does not substitute for the knowledge and judgment of your health care professional.biz/PharmaceuticalDossier.

Do not crush. headache. Measure the liquid medication with the provided dose-measuring spoon/dropper to make sure you have the correct dose. remember that he or she has judged that the benefit to you is greater than the risk of side effects.XYZ PHARMACEUTICAL This drug is used to treat mild to moderate pain (e. or nausea/vomiting). Many people using this medication do not have serious side effects. new signs of infection (e. seek immediate medical attention. (See also Side Effects and Precautions sections. If you are uncertain about any of the information. chew or allow to dissolve on the tongue. Read the dosing instructions carefully for each product because the amount of acetaminophen may be different between products. If you think you may have a serious medical problem. For chewable tablets. fever. Seek immediate medical attention if you have 77 Contact :: info@icpc. For adults.. Tell your doctor if your condition persists or worsens or if you develop new symptoms. do not take this product for pain for more than 10 days (5 days in children) unless directed by your doctor. swallow the medication whole. Pain medications work best if they are used as the first signs of pain occur. If your doctor has directed you to use this medication. headaches. the medication may not work as well. then swallow with or without water. If you are using sustained-release tablets.g. consult the doctor promptly. For rapidly-dissolving tablets.g.. or break the tablets.aspx . the maximum dose of acetaminophen for adults is 4 grams per day (4000 milligrams).) Do not take this medication for fever for more than 3 days unless directed by your doctor.biz Website :: http://icpc. chew thoroughly before swallowing. There are many brands and forms of acetaminophen available. The maximum dose of acetaminophen for children is based on age/weight (check product package for details). Do not use a household spoon. chew.biz/PharmaceuticalDossier. Taking more than the maximum daily amount may cause serious (possibly fatal) liver disease. HOW TO USE: Take this product by mouth as directed. consult your doctor or pharmacist. SIDE EFFECTS: Tell your doctor immediately if any of these rare but very serious side effects occur: easy bruising/bleeding. shake the bottle well before each dose. For suspensions. Doing so can destroy the long action of the drug and may increase side effects. If you do not have liver problems. If you wait until the symptoms have worsened. persistent sore throat). Follow all directions on the product package. cold/flu aches and pains) and to reduce fever. If the child has a sore throat (especially with high fever. Do not take more acetaminophen than recommended.

consult your doctor or pharmacist before using this product: liver disease. phenobarbital). carbamazepine.. Acetaminophen may cause liver damage. Contact your doctor for medical advice about side effects. isoniazid. DRUG INTERACTIONS: If you are taking this product under your doctor's direction. Acetaminophen passes into breast milk. tell your doctor or pharmacist if you are allergic to it. The following numbers do not provide medical advice. However. seek immediate medical attention if you notice any symptoms of a serious allergic reaction. phenothiazines (e. chlorpromazine). trouble breathing. severe dizziness. or if you have any other allergies. tell your doctor or pharmacist if you use any of the following products: anti-seizure medications (e. phenytoin. dark urine. Consult your doctor before breast-feeding.biz/PharmaceuticalDossier. If you have phenylketonuria (PKU) or any other condition that requires you to restrict your intake of aspartame (or phenylalanine). consult your doctor or pharmacist about using this drug safely. contact your doctor or pharmacist.XYZ PHARMACEUTICAL any of the following symptoms of liver damage: persistent nausea/vomiting. your doctor or pharmacist may already be aware of possible drug interactions and may be monitoring you for them. including: rash. regular use/abuse of alcohol. If you have any of the following health problems. especially when combined with acetaminophen. extreme tiredness.aspx . This children's form of this medicine may contain aspartame. or change the dosage of any medicine before checking with your doctor or pharmacist first. Do not start. Ask your doctor or pharmacist about using this product safely. "blood thinners" (e. This is not a complete list of possible side effects. stop. stomach/abdominal pain. Liquid forms of this product may contain sugar. Before using this product. warfarin). 78 Contact :: info@icpc. A very serious allergic reaction to this drug is rare.biz Website :: http://icpc.. Caution is advised if you have diabetes.. If you notice other effects not listed above. yellowing eyes/skin. but in the US you may report side effects to the Food and Drug Administration (FDA) PRECAUTIONS: Before taking acetaminophen. itching.g. Tell your doctor if you are pregnant before using this medication. Daily use of alcohol may increase your risk for liver damage. swelling.g. Ask your doctor or pharmacist for more information.g.

extreme tiredness. contact your local poison control center or emergency room immediately. increased sweating. STORAGE: Store at room temperature between 68-77 degrees F (20-25 degrees C) away from light and moisture. Consult your doctor for more details and to see which medication might be right for you.biz Website :: http://icpc. fever reducers.) This medication may interfere with certain medical/laboratory tests (including urine 5-HIAA). (See also maximum daily dose information in Side Effects section. Canada residents can call a provincial poison control center. skip the missed dose and resume your usual dosing schedule. Do not double the dose to catch up. US residents can call the US National Poison Hotline at 1-800-222-1222.XYZ PHARMACEUTICAL Acetaminophen is an ingredient in many nonprescription products and in some combination prescription medications. Do not store in the bathroom. dark urine. This document does not contain all possible interactions. Do not flush medications down the toilet or pour them into a drain unless instructed to do so. OVERDOSE: If overdose is suspected. ibuprofen. vomiting. take it as soon as you remember. Consult your pharmacist if you are uncertain whether your other prescription or nonprescription products contain acetaminophen. Read the labels carefully before taking other pain relievers. yellowing eyes/skin. Make sure laboratory personnel and all your doctors know you use this drug. and naproxen may cause. Symptoms of overdose may include: nausea. possibly causing false test results.aspx . severe stomach/abdominal pain. Therefore. However. before using this product. NOTES: Acetaminophen does not cause the stomach and intestinal ulcers that NSAIDs such as aspirin. Keep a list of all your medications with you. Properly discard this product when it is expired or no longer needed. MISSED DOSE: If you miss a dose. If it is near the time of the next dose. and share the list with your doctor and pharmacist. acetaminophen does not reduce swelling (inflammation) like the NSAIDs do. Keep all medicines away from children and pets. or cold products to see if they also contain acetaminophen. Consult your pharmacist or local waste disposal company for more details about how to safely discard your product. 79 Contact :: info@icpc.biz/PharmaceuticalDossier. tell your doctor or pharmacist of all the products you use.

aspx .biz/PharmaceuticalDossier.biz Website :: http://icpc.XYZ PHARMACEUTICAL CTD Module III COMPOSITION 80 Contact :: info@icpc.

00 4.00 6.00 620.00 5. II 1 2 3 4 5 6 7 Name ACTIVE SUBSTANCE(S) PARACETAMOL EXCIPIENT(S) LACTOSE MICRO CRYSTALINE CELLULOSE STARCH MAGNESIUM STEARATE SODIUM STARCH GLYCOLATE COLLOIDAL SILICON DIOXIDE PURIFIED TALC TOTAL 23.biz 81 Website :: http://icpc.aspx .XYZ PHARMACEUTICAL III A COMPOSITION QUALITATIVE AND QUANTITATIVE COMPOSITION EACH TABLETS CONTAINS Nº I 1.00 5.00 mg mg mg mg mg mg mg MG BP BP BP BP BP USP BP Quantity 500.biz/PharmaceuticalDossier.00 Unity mg Reference BP II A 2 CONTAINER Blister of10Tablets Such 10 Strips in Box Such 250 Box In 7 Ply Corrigated Box 20 GSM Paper Contact :: info@icpc.00 27.00 50.

XYZ PHARMACEUTICAL PREPARATION METHOD Contact :: info@icpc.aspx .biz/PharmaceuticalDossier.biz 82 Website :: http://icpc.

00 6.00 50.biz/PharmaceuticalDossier.00 5.aspx .XYZ PHARMACEUTICAL II B METHOD OF PREPARATION II B 1 MANUFACTURING FORMULA (INCLUDING DETAILS OF BATCH SIZE) EACH TABLETS CONTAINS Nº I 1.00 5.00 4.00 620.00 mg mg mg mg mg mg mg MG BP BP BP BP BP USP BP Quantity 500.00 27.biz 83 Website :: http://icpc. II 1 2 3 4 5 6 7 Name ACTIVE SUBSTANCE(S) PARACETAMOL EXCIPIENT(S) LACTOSE MICRO CRYSTALINE CELLULOSE STARCH MAGNESIUM STEARATE SODIUM STARCH GLYCOLATE COLLOIDAL SILICON DIOXIDE PURIFIED TALC 23.00 Unity mg Reference BP Contact :: info@icpc.

Tablets PACKING STYLE: 10X10T Theoretical Yield: Final Batch Size=100.biz 84 Website :: http://icpc.XYZ PHARMACEUTICAL BATCH MANUFACTURING & PACKING RECORD TABLET SECTION Product Name: PARACETAMOL TABLTET 500 MG Generic Name: PARACETAMOL TABLTET 500 MG Product Code: FPA376 Std. : MFC/ FPA376 BMPR.: 01 of 30 Label Claim: EACH UN COATED TABLET CONTAINS: PARACETAMOL BP ---------500 MG EXCIPIENTS-------------------------Q.000 TABLETS Mfg. Started on: Issue By: Mfg. Lic. No. 00.No: BMPR/ FPA376 Mfg.aspx . Effective Date: Recoverable Residue Added: Kg.: Mfg. Batch Size: 1. Completed On: Date: Review Date: Two years MFC. Date: Standard Self Life: 36 months Page No. No. : Batch No. HEAD (SIGN & DATE) Contact :: info@icpc.A.S.000 TABS. TENTATIVE BMPR FOR FIRST THREE BATCH FINAL DOCUMENT VARIFIED BY: ____________________ PRODUCTION HEAD (SIGN & DATE) _____________ Q. Date: Exp.biz/PharmaceuticalDossier.

surgical gloves and any other safety provisions must be followed.biz/PharmaceuticalDossier. Protective mask.XYZ PHARMACEUTICAL PRE-MANUFACTURING AND PACKING CONTROL OPERATION: 1 Carry out all the activities related to equipment cleaning and material handling strictly as per respective standard operation procedure and cleaning schedule. Contact :: info@icpc. 2 3 4 Maintain labels of in process stages.aspx . Get QA clearance before beginning of each operation. All personnel must observe stipulated gowning code for respective area.biz 85 Website :: http://icpc. Label all the recoverable and non-recoverable materials clearly and prominently. Dispose the materials as per standard operating procedure. Check and record temperature and humidity of every room. Label all equipments and areas with status and product label and display prominently. 5 6 7 8 9 Any deviation /from the MFC must be done with prior approval of QA by deviation request.

Qty (Kg) Ov.R.000 ____ BINDER 05 06 -15.300 1. Received Kg.XYZ PHARMACEUTICAL MATERIAL ISSUING & DISPENSING CHECKING RECORD Sr. A.00 4. (D)$ = Quantity to be compensates on increasing quantity of active material. CHE CKE D BY DRY MIX 01 02 03 04 500 ---500 50 23 12 PARACETAMOL (B)* MCCP Lactose Starch 1RAA376 BP. BP 1RIM103 1RIL101 1RIS105 5. % Qty. Qnty.00 5. No Label Clai m (mg) Qty/ Tab. to be calculated on basis of % Assay.200 _____ ____ ____ 50.000 2. BP. NO.00 6.500 0. (mg) INGREDIENTS Spec. Contact :: info@icpc.500 ____ ____ ____ ____ (B)* = Quantity maintain on 100% Assay.600 0.biz/PharmaceuticalDossier.biz 86 Website :: http://icpc.400 0.00 ____ Starch Purified Water BP BP 1RIS105 1RIP105 0.00 620 Magnesium Stearate Talc. Item Code Std.S ____ ____ LUBRICANTS 07 08 09 10 ----TOT AL 5. BP.500 Q.aspx . (D)$ Sodium Starch Glycolate Colloidal Sillicon Dioxide BP BP BP USP 1RIM101 1RIT101 1RIS103 1RIC105 0.

PARACETAMOL required per batch =L.XYZ PHARMACEUTICAL 1) RAW MATERIAL REQUIREMENT CALCULATION : (I) PARACETAMOL: (For Single A. : ____________% (Cw) – Water of PARACETAMOL From 1st A.R.R. required From 2nd A.No. of PARACETAMOL required per tablet = L.R.R.No.aspx .R.Claim x 100 x 100 = (C) x (100 – Cw) Qty. From 1st A. Required = (H) x {C x (100 . of Talcum require/ batch = ______________Kg.R.R.No. Total Qty.R. x + x = Kg.No.M required From 2nd A.claim x B. (B)* Deduction quantity of Talcum required: (B)* – T = _____-_______= _______kg (P) Inactive Raw material Calculation Adjusted for increasing Active addition : Theoretical qty.) Assay of Raw material (Cn) & (Dn) (C) – Assay of PARACETAMOL From 1st A.) Theoretical Qty.R. ( I ) R.R.No.biz 87 Website :: http://icpc. Req. : ____________% (E) – Available Stock ofPARACETAMOL From 1st A. (G) – (E) = _____ -_____ = x 100 x 100 = x (100 ) ____ = mg / tablet(Fn) Kg. (A) = x_______ 1000000 Kg. = L. 100 x 100___ x ( 100 ) mg.R.No.No.No. Req.A : Contact :: info@icpc.Cw)} = {(D) x (100 . : ____________% (Dw) – Water of PARACETAMOL From 2nd A.=__________Kg.No. (H) Qty.Claim x 100 x 100 Assay X (100-water) = = = (A) x Batch Size 1000000 = (I-A) PARACETAMOL: (For Double A./Batch From 1st A. Required / Batch = (E) + ( I ) =      . / Batch (B)* x 1000000 ___________Kg. Quantity of PARACETAMOL Required. : ________________ Kg.biz/PharmaceuticalDossier. : ____________% (D) – Assay of PARACETAMOL From 2nd A.No./Batch = (Fn) x Batch Size = From 1st A.No.No. (G) Qty. Actual Qty.Size =_______Kg/ Batch 1000000 (T)  Qty.Dw)} From 2nd A.No. ( C ) Actual quantity of Talcum require / batch = C – P =___________Kg (D)$ CHECKED BY : Production : Q.R.R. 1000000 Now.

Relative Humidity: 3 Differential Pressure: 4 DETAILS OF PREVIOUS PRODUCT: Name of Previous product : Batch No. Contact :: info@icpc.) Done By Checked by : Q.aspx .XYZ PHARMACEUTICAL EQUIPMENT / AREA / LINE CLEARANCE: GRANULATION Sr. : 40%. Chemist Date & Time.) Two Pan Balance(5 Kg) Sieve 20.biz 88 Website :: http://icpc.A. No. Temperature °C : 2. Operation SOP Cleaning SOP Done By Checked By GRANULATION: I 1 2 3 4 5 6 7 Sifter Planetary Mixer Fluid Bed Dryer Multi Mill Yard Balance (300 kg.biz/PharmaceuticalDossier. Equipment Equipment No. : Production Chemist Date & Time. LIMIT Date & Time: Date & Time: Date & Time: (27°C ±3°C ) (50% ±5 Rh) ( 10-15 PSI ) LINE CLEARANCE (AREA & MACHINERY.F T0201 T0202 T0203 T0204 T0103 T0104 T0210 T0205 T0206 T0207 T0208 T0103 T0104 T0210 ENVIRONMENT CONTROL 1.40 # E/01 E/02 E/03 E/04 E/25 E/26 E/01-E.

as per Store’s Requisition Cum Issue Slip. Mask.XYZ PHARMACEUTICAL cePRE MANUFACTURING CONTROL OPERATIONS: 1 2 3 4 Sr. SIFTING: Note: PassPARACETAMOL through 20# sieve.add this starch slurry in Boil Mix well for homogeneous. 3. Control no. For operation & cleaning of machines follow respective SOP‘s. Take starch & Add Purified water and make slurry with stirring. 4. date.biz 89 Website :: http://icpc. Lactose Starch Through 30# Sieve integrity Checked (b) Before use: Date: (c) After Use: Date: MIXING: Transfer above sifted material (STEP-2) in planetary mixer bowl and mix for 10 minutes at slow speed. date. Boil it.0 Contact :: info@icpc. Obtained line clearance from Quality Assurance department before starting the activity. gloves. Exp. No.biz/PharmaceuticalDossier. CHECKED BY 1.0 PREPARATION OF GRANULATING PASTE: Take 8 Lits purified water in s. Mfg. Always take care to avoid cross contamination of material. 2. Any deviation from the MFR must be done with prior approval of Q.aspx . vessel. Use proper uniform. & safety goggles. while handling raw materials..s.A on deviation request PROCESS DATE TIME DONE BY WEIGHING AND CHECKING : Check the weight of all (active/inactive) raw materials and their name. Pass MCCP.

Check the granules LOD % in IR Moisture balance..0 mm sieve in Multimill Mill Knives forward. tablets.XYZ PHARMACEUTICAL SR.biz/PharmaceuticalDossier. inspection rejections and other recoverable Residues are to be added in nex 1. Dt. MFG. DATE EXP.0 PROCESS RECOVERABLE RESIDUE : Machine setting granules. Dt. 4 Retest recoverable Residue after was six month & use with in one year.aspx . 5.DATE Total Qty: 5.Exp. Mfg.8 Screen Inspected by : Before Use : After Use Contact :: info@icpc. And respective qty. NO. 5 Record the details of Reprocessible materials added with details of Batch No..biz 90 Website :: http://icpc. added. 2 Blend with the granules during Dry Mixing 3 “Recoverable Residues” should not be more than 5% w/w of Batch Size. 6. Mill the tablets using 2. DATE TIME DONE BY Batch No..

) till Mass is dry For about 30 min trolley 2 Dry using hot air 40°C (without starting Heater. 6.0 L.) till Mass is dry For about 30 min 8. Check the mass for binding.XYZ PHARMACEUTICAL SR. Note down qty. Added qty of Purified water BP : 12.0liter Actual Time : min. Contact :: info@icpc. Observed : (NMT 3% ) DRY SIEVING : Sift the dried granules through 20# sieve in Sifter and collect sifted granules in a poly bag kept in a plastic drum. NO. 7. Sieve integrity Checked by : (before) Sieve integrity Checked by : ( after).biz 91 Website :: http://icpc.O.5) in FBD 30KG trolley 1 &2 Trolley 1. of Purified Water BP added.D.0 DRYING : Transfer above binded mass (step 4.biz/PharmaceuticalDossier. Dry using hot air 40°C (without starting Heater.0 PROCESS DATE TIME DONE BY CHECKED BY GRANULATION: Slowly add paste (step4) to the dry mixed powder in PLM and granulate for 10 minutes at slow speed. Add Purified Water BP if required.aspx .

NETT WT. Total Wt. 1. Percentage yield: (Yield should not be less than98. 3.aspx . investigate. : Kg DRIED GRANULES RECONCILIATION DRUM NO. Theoretical Wt. wt. of granules: Kg. Kg. No.0 PROCESS DATE TIME DONE BY CHECKED BY MILLING:Collect the over size granules and mill using 2 mm sieve. of granules: Kg. Kg.5%) Remarks: If any deviation in % yields.biz/PharmaceuticalDossier. : Kgs. Kg. Actual wt. Theo. 9.XYZ PHARMACEUTICAL Sr. TARE WT. Collect the milled granules and add to the sifted granule of ( step 7) Screen inspected By: Before Use:__________ After Use:_________ Weigh the total granules obtained. 2.biz 92 Website :: http://icpc. knife forward and at slowest speed through Multi Mill. GROSS WT. Contact :: info@icpc.

3. Kg. Kg. GROSS WT.XYZ PHARMACEUTICAL SR. 2. Theo. lubricant in PLM add Reprocessible material and lubricate for 10 minutes at slow speed. NETT WT. : Contact :: info@icpc.aspx .biz 93 Website :: http://icpc.biz/PharmaceuticalDossier. LUBRICATED GRANULES RECONCILIATION DRUM NO. 1. Percentage yield : % ( Yield should not be less than 98. Sieve integrity Checked By Ok (After) Transfer dry granules (Step-7). Kg.5%) Remarks: If any deviation in % yields. PROCESS DATE TIME DONE BY CHECKED BY 10.0 FINAL MIXING : (LUBRICATION ) Sieve integrity Checked by (sign) Ok (Before) sift following material through 40 # after mixing Magnesium Stearate BP Talc BP Sodium Starch Glycolate BP on Sifter and collect in a poly bag. Total Wt. Actual wt. investigate. of lubricated granules : Kg. wt. of granules : Kg. NO. TARE WT.

Affix “UNDER TEST SLIP” from Q.aspx . Release given by : : : % % (Limit: 95. Dept on drum(s) and tightly close the drum(s). Moisture of granules Q. Assay 2.C.0%) (Limit : NMT 3% ) Date Time : Affix a suitable label on drum when batch sample is approved by Q. Contact :: info@icpc.C.C. Q.C.biz/PharmaceuticalDossier. RESULTS 1.0% to 105.biz 94 Website :: http://icpc.XYZ PHARMACEUTICAL TEST REQUEST Bulk sample drawn by (Sign): Date : Quantity: Time : Gms.

SOP No.7 mm Round Die: 12. Clean.SOPNo. No. 4 Temperature: Relative Humidity: Differential Pressure: C. T0302 T0303 Done by Check by Rotary Tablet Compr.aspx .) Done By : _______________ Production Chemist Date & Time.biz 95 Website :: http://icpc.7 mm Round 4 Two Pan Balance (Analytical) E/25 T0105 5 Single Pan Balance (Analytical) E/27 Q0502 6 Disintegration Test Apparatus E/11 QO504 7 Vernier caliper E/09 QO517 8 Hardness Tester E/08 QO514 9 Friability Test Apparatus E/10 QO503 10 De-duster E/33 T0304 LINE CLEARANCE (AREA & MACHINERY. 1 Equipment No. 2. T0105 Q0502 QO504 QO517 QO514 QO503 T0304 Contact :: info@icpc. Chemist Date & Time.A. : Equipment Used Production Chemist: Ope.: 1.biz/PharmaceuticalDossier. 12. Date & Time: Date & Time: Date & Time: (27°C ±3°C) (50% ±5 Rh) (10 to 15 PSI) DETAILS OF PREVIOUS PRODUCT: Name of Previous product: Batch No. Checked by : _______________ Q. Checking integrity of Die-Punch Upper Punch Checked by : Lower Punch Dies Sr. Machine1 E/05 T0301 (16 stn.XYZ PHARMACEUTICAL TABLET COMPRESSION PROCESS: - Compression started Date : ENVIRONMENT CONTROL COMPRESSION MACHINE NO. 3.) 3 Punch Set :16/32” mm Round E/07 T0303 Upper Punch 16/32” mm Round Lower Punch .

Particular batch will be segregated by a partition. wt. THICKNESS 5. PRECAUTIONS: Check the department as well as machine for cleanliness & line clearance. Max. The containers will be placed in such a way that all the container labels are facing the individual inspecting the batch. : (27ºC ±3ºC) Humidity: 50% ±5%Rh) (1) (2) (3) (4) (5) (6)  Sr. of Punch Weight in mg. stage.biz 96 Website :: http://icpc. Confirm release for compression. ± 3 %  IN-PROCESS PERAMETERS TO BE CHECK DURING COMPRESSION : CHECKING FREQUENCY Every 30 minutes. No. No.aspx . Every 2 hours. Every 2 hours. Machine & Floor should be kept in clean condition. (9) Environment control: Room Temp. of Punch Weight in mg. ± 5 % GM. NMT 15 MIN. WEIGHT OF 20 TABLETS 2. HARDNESS 2-5 KG/CM². INDIVIDUAL WEIGHT OF TABLET 3. wt.. etc. Min. (7) The compressed tablets are stored in the poly-bags in the containers to approximately 80 to 90% of the holding capacity of the poly-bag to facilitate proper tying with twine. date. wt. MM ± 0. PARAMETER LIMITS Contact :: info@icpc. No. Operator should wear full sleeve hand gloves and nose mask. Avg. Every 2 hours. Limit Min. The containers will be stored on pallets in rows with the maximum height of 2 containers.biz/PharmaceuticalDossier.2 MM MG. 1. Affix a status label indicating Product Name.XYZ PHARMACEUTICAL  INITIAL COMPRESS CHECK RECORD: 1 11 Max. B. Every 2 hours. Limit 2 12 3 13 4 14 5 15 6 16 7 8 9 10 No. DISINTEGRATION TIME 4. (8) Follow the respective SOPs of equipment.

aspx . FRIABILITY NMT 1 %. Contact :: info@icpc.XYZ PHARMACEUTICAL 6.biz 97 Website :: http://icpc.biz/PharmaceuticalDossier. Every 2 hours.

Contact :: info@icpc.2 mm.XYZ PHARMACEUTICAL DATE TIME Wt .of 20 tabs .aspx . NMT 15 MIN Hardness Kg/cm².biz 98 Website :: http://icpc.biz/PharmaceuticalDossier.T. Friability NMT 1. gm ± 3% D.0 % Checked By & Sign. Thickness ± 0.

Wt. : ______g % = Contact :: info@icpc. of 20 Tab(before): b. : % a. Wt. : % = a.aspx . : % FRIABILITY – 4 Date : Time : FRIABILITY – 5 Date :______ Time :______ FRIABILITY – 6 Date :______ Time :______ a. Wt. Wt. Diff. Diff. : ______g % = a. Wt.of 20 Tab(before): b. Wt. of 20 Tab (after) : c. of 20 Tab(before): b. Diff.biz/PharmaceuticalDossier. Wt. Diff. Wt.of 20 Tab (after) : c.biz 99 Website :: http://icpc. of 20 Tab (after):______g c. : % = a. Wt. Wt. Diff. of 20 Tab (after) : c.of 20 Tab(before): b. Wt. of 20 Tab (after) :____g c.of 20 Tab(before):_____g b.XYZ PHARMACEUTICAL FRIABILITY % = c x 100 a FRIABILITY – 1 Date : Time : Date : FRIABILITY – 2 Time : Date : FRIABILITY – 3 Time : a. Wt.of 20 Tab (after): c. of 20 Tab(before):____g b. Diff.

in Mg. ) Av. investigate. Kg. 1 11 1 11 2 12 2 12 3 13 3 13 4 14 4 14 5 15 5 15 6 16 6 16 7 17 7 17 8 18 8 18 9 19 9 19 10 20 10 20 Weight of 20 Tabs. 2. Net wt. Av.XYZ PHARMACEUTICAL RECORD OF WEIGHT VARIATION (FREQUENCY EVERY 2 HOURS. Wt.biz 100 Website :: http://icpc. Kg. Kg. Kg.biz/PharmaceuticalDossier. Kg. Tare wt. Drum No. wt. in Mg. Kg. = 620 mg Limit: 5 % (_589 mg to 651mg) Date: Time: Date: Time: INDIVIDUAL WEIGHT – 1 INDIVIDUAL WEIGHT – 2 No Weight in No Weight No Weight No Weight in Mg. 1.= B (Limits : NLT 98. in Mg. (A) Theoretical batch size = (B) Weight of granules transferred = (C) Weight of compressed tablets = (D) Recoverable residue = (E) Rej. Total weight : Rejection Destroyed by : Kg Checked by : Date : Contact :: info@icpc. Av. Kg. for destruction = C+ D X 100 % Yield = --------------------. Mg. Wt. Per Tablet: Max mg & Min Sign :_______________ gm mg mg  Date: Time: INDIVIDUAL WEIGHT – 3 No Weight No Weight in Mg. % w/w. Per Tablet: Max mg & Min Sign :_______________ gm mg mg Weight of 20 Tabs Av. Per Tablet: Max mg & Min Sign :_______________ Weight of compressed tablets with yield.00%) Note : If yield is less than limit. Wt. per Tab. Gross wt. Kg.aspx . 1 11 2 12 3 13 4 14 5 15 6 16 7 17 8 18 9 19 10 20 gm mg mg Weight of 20 Tabs.

ITEM CODE STD. Kg.NO.biz 101 Website :: http://icpc.R.aspx . Total weight : Kg PACKING:  PACKING MATERIAL REQUISITION WITH SPECIFICATION : Packing Material Issue Date: 4/12/08 SR. Kg. NO. Picking. 1. ITEM SPEC. QTY. Kg. RECEIVED CHECKED BY Plastic small tin Printed labels Corrugated box IHS IHS 2PTC376 2PLC376 IHS 2CBC376 EQUIPMENT NO. 2. Remark :Take 100 Tablets for inspection of physical parameters such as mottling . NAME OF THE MACHINE Coding M/C Box Strapping M/C Contact :: info@icpc. CLEANING T0503 SR. 2. 3. softening of tablets. 1. 2. capping. Tare wt.NO. E/20 E/21 20 CAPACITY SOP NO. sticking. Gross wt.XYZ PHARMACEUTICAL CORE TABLETS INSPECTION. OPERATION HAND HAND T0503 T0504 T0504 SOP. Inspected By : Date & Time Supervised By. If deviation that occurs more than 2 % take whole batch for inspection WEIGHT OF INSPECTED TABLETS Drum No. Net wt. Rejection for Destruction: = Destroyed By: Pankaj Recoverable residue = Kg. NO 1.biz/PharmaceuticalDossier. QTY 1000 1030 A.

APPROVED BY Q.C. Reconciliation of packing material should be done after packing is finished.A.T0503-01 Obtain Line clearance from Q. 7. “Line clearance” should be performed as per SOP no. department is to be confirmed before packing operation started. No. 5. 2.aspx . 4. 8. Over printing on carton and catch cover should be done in advance. b) Now start Labels printing m/c as per SOP No. 7. “Release Notice” from Q.C. PRECAUTIONS : Environment control (Packing room):-Temp: 27C±3C Humidity: 50% ± 5 % R. 10. 6.Q0714 Rejection and recoverable rejection strips should be kept in separate with proper label. Rejection material should be destroyed and carried to scrap and record accordingly.T0503-01 DATE TIME FROM TO CHECKED BY PROD. 3. Q0737 (Equipment) Over printing should be checked carefully by packing supervisor and department in charge and counter Checked by Q. 4.A Contact :: info@icpc.. 6.  CODING MATTER ON LABELS : PROCESS a) Set Labels printing m/c as per SOP No.XYZ PHARMACEUTICAL  1.A. 3. 8. 1. 9. Approved the label for coding matter by Q. Leak test should be performed before starting packing line and confirmed for sealing as per SOP no.A SR. CHECKS General Cleanliness Machine / Equipment Cleanliness ( Visual Checking ) previous product / material Stereo of previous product Check print matter on carton Status label on packing line Release status of issued packing material BMPR Status Log Card entry Line Clearance label Note : Line Clearance is required if work continues for next day.biz 102 Website :: http://icpc.biz/PharmaceuticalDossier.  LINE CLEARANCE CHECK LIST : OBSERVATION CHECKED BY PRODUCTION Q. 5.H. department. 2.

biz 103 Website :: http://icpc.A) : Contact :: info@icpc. : (INCLUSIVE ALL TAXES)  SPECIMEN OF PRINTED LABELS : PRINTED BY CHECKED BY PROD APPROVED BY Q.aspx . DATE : CHECKED BY (PROD) : MFG. DATE : EXP. : MAXIMUM RETAIL PRICE Rs.A NAME OF PRODUCT : PARACETAMOL TABLET 500MG BATCH No. : MFG.XYZ PHARMACEUTICAL CODING DETAILS ON LABELS BATCH NO. DATE : MAXIMUM RETAIL PRICE Rs. DATE : APPROVED BY (Q. : (INCLUSIVE ALL TAXES) EXP.biz/PharmaceuticalDossier. : MFG.No.LIC.

biz/PharmaceuticalDossier.S. Packed Checking Counting Labeling 7plyouter corr.aspx .R. sent to B. Packed = Total Qty.A Contact :: info@icpc. = Tablet Control Sample: Tablet Tablet CHECKED BY PRODUCTION : PPROVED BY : Q.box filling Total Qty.XYZ PHARMACEUTICAL REMARKS : Date Time Qty.biz 104 Website :: http://icpc.

Issued (B) Qty.XYZ PHARMACEUTICAL PACKING MATERIAL RECONCILIATION: Packing Material Qty. For Labels ± 3. Required (A) Qty. : Qty.biz/PharmaceuticalDossier. CHECKED BY PRODUCTION Qty.biz 105 Website :: http://icpc. : Tablet Date : Date : Contact :: info@icpc.A Retain sample Qty. Used (C) Quantity Destroyed (D) Qty. Transferred to Finished goods Warehouse: Goods transfer slip no. packed : : APPROVED BY : Q.aspx .0%. Returned (E) Total Consumption (F) C+D Difference B-(F+E) % Deviating (B-F)X100 B Acceptance criteria: Printed Labels Plastic tin Online Rej.

Qty. Gm.XYZ PHARMACEUTICAL BATCH RECONCILLIATION RECORD: 1.aspx . = : Tablets. Actual Batch Size 2.4 Retain Samples 3. Kg. 2. Samples For Analysis 2.biz/PharmaceuticalDossier.050 : 100 Tablets. Kg. Of Inprocess Sample : : : 0. Percentage Yield (2 + 3 + 4 ) ------------------.A Contact :: info@icpc. Total Quantity Destroyed : At Granules Stage: : At Compression Stage 6.3 Tablets For Finished Product Analysis : 120 2.1 Granules For Bulk Analysis 2.2 Qty. 3X100Tablets.0% ) Please Investigate.X 100 (1 ) Note: If Yield Is Less Than CHECKED BY : PRODUCTION = % ( Limits : NLT 97. Tablets. Tablet Tablets.biz 106 Website :: http://icpc. 100000 100 Gm = 80 Tablets. APPROVED BY : Q. Of Recoverable Residue: 4 Quantity Transferred To Finished Goods Warehouse 5. Tablets.

XYZ PHARMACEUTICAL DEVIATION REPORT Contact :: info@icpc.biz 107 Website :: http://icpc.aspx .biz/PharmaceuticalDossier.

WEIGHING SHIFTING MIXING GRANULATION SEMI DRYING SIFTING QUALITY CONTROL FINAL DRYING PACKING LUBRICATION COMPRESSION Contact :: info@icpc.biz/PharmaceuticalDossier.biz 108 Website :: http://icpc.XYZ PHARMACEUTICAL FLOW CHART FOR MANUFACTRUING PROCESS OF TABETS R.M.aspx .

XYZ PHARMACEUTICAL Finished product specification Contact :: info@icpc.biz 109 Website :: http://icpc.biz/PharmaceuticalDossier.aspx .

620gm (±5. Incharge Approved By Q.400 gm 0.1 mm ) 3.XYZ PHARMACEUTICAL FINISHED PRODUCT SPECIFICATION QUALITY ASSURANCE DEPARTMENT FINISHED PRODUCT SPECIFICATION Issue No : 01 First Issue Date: Dosage Form: Tablet Product Name:PARACETAMOLE TABLET 500 MG Generic Name: PARACETAMOLE TABLET 500MG Revision No Revision Date: Specification No : Page 1 of 1 Tested as per : BP Mfg. of sample should same as sample in assay test NMT 8 Mins 97.0 – 105. 12.A.biz 110 Website :: http://icpc.7 mm ( ± 0.T. Pharmacopial NA NA NA NA NA NA NA ± 7.5 – 7. Lic. : CATEGORY: ANALGESIC & ANTI PYRETICS.4 mm ) 12. Finished Product Requirement 12.0 % white. of sample should same as sample in assay test NA 97. Wt.T. Chemist Checked By Q.aspx .620 gm NA NA NA NA NA R.M.biz/PharmaceuticalDossier.4 mm ) 12.T. round. of sample should same as sample in assay test NMT15Mins 90. EACH UN COATED TABLET CONTAINS PARACETAMOL BP Sr Test / Parameter Bulk 01 02 03 04 05 06 07 08 09 Description Wt.0 % 10 11 Disintegration Time Assay of PARACETAMOLE NA = NOT APPLICABLE Issued By Q.A.0 % Uncoated 500 mg.0 – 103.7 mm ( ± 0.0 %) NA 4.0 % R. uncoated tablet . Self-Life: 3 years or depending upon the self-life of active ingredient.7 mm ( ± 0. un coated tablet. which ever is less Storage Condition: In a cool & dry place. of sample should same as sample in assay test NMT 10 Mins 95. 1.0 – 110 % In-House Awhite colour round.T. Manager Contact :: info@icpc.1 mm ) NA ± 5.T.400 gm (±5. Of tablet Friability Thickness Diameter Hardness Uniformity of weight Identification Off white Coloured granule 12.5% R. Of 20 tablets Av.400 gm 0.0 – 103.620 gm N.7 mm ( ± 0.0 % R.A.0 kg/cm2 ± 5.0 %) 0.0% 4.

aspx .biz/PharmaceuticalDossier.biz 111 Website :: http://icpc.XYZ PHARMACEUTICAL Method Of Analysis of Finished Products Contact :: info@icpc.

biz/PharmaceuticalDossier.7 mm + 0.biz 112 Website :: http://icpc.XYZ PHARMACEUTICAL SUBJECT DEPARTMENT PRODUCT NAME GENERIC NAME FPS NO.0 Kg/ cm2 : 4. QUALITY CONTROL. It one or two on 12 additional tablets. Contact :: info@icpc.5 g of Paracetamol with 20 ml of acetone. not less than 16 of the total of 18 tablets disintegrate completely.aspx .Disintergration : NMT 15 MIN Place one tablet in each of the six tubes of the basket. Appendix II A. lift the basket from the fluid and completely. 2. Average weight Hardness Thickness : 620. 4. is concordant with the reference spectrum of paracetamol (RS 258). add a disc to each tube and operate the apparatus using water maintained at 37°+ 2 c as the immersion fluid. PARACETAMOL TABLETS PARACETAMOL TABLETS BP 500 MG FPS/PARA-500/01 01/01/2004 SUPERSEDES : --PAGE NO. Description: White round flat bevel. uncoated tablet with break line on one side.Identification Extract a quantity of the powdered tablets containing 0. The residue complies with the following tests. : 01 / 05 EFFECTIVE DATE 1. A.0% 3. : : : : : : FINISHED PRODUCT METHOD OF ANALYSIS.00mg + 5% : NLT 3. evaporate the filtrate to dryness and dry at 105°. filter.4MM Friability : NMT 1. The infrared absorption spectrum. at the end of 15 minutes.

Add 0.XYZ PHARMACEUTICAL SUBJECT DEPARTMENT PRODUCT NAME GENERIC NAME FPS NO.05 ml of 0. 15 volumes of methanol and 85 volumes of water as the mobile phase with a flow rate of 2 ml per minute and (c) a detection wavelength of 272 nm.001% w/v of 4-amino-phenol in methanol (15%). Solution (1) contains 0. 4 . about 169° 5.0 g of Paracetamol with 15 ml of methanol . Appendix III D.biz/PharmaceuticalDossier.4 volume of formic acid.01M sodium butanesulphonate in a mixture of 0. : : : : : : FINISHED PRODUCT METHOD OF ANALYSIS.biz 113 Website :: http://icpc. using the following solutions.6 mm) packed with stationary phase C (10 µm) (Nucleosil C18 is suitable). PARACETAMOL TABLETS PARACETAMOL TABLETS BP 500 MG FPS/PARA-500/01 01/01/2004 SUPERSEDES : --PAGE NO. (b) 0.AMINOPHENOL Carry out the method for liquid chromatography.1 g with 1 ml of hydrochloric acid for 3 minutes. a violet colour is produced slowly which does not turn red. The chromatographic procedure may be carried out using (a) a stainless steel column (20 cm × 4. QUALITY CONTROL. For solution (2) shake a quantity of the powdered tablets containing 1.aspx . Contact :: info@icpc. : 02 / 05 EFFECTIVE DATE B. add 10 ml of water and cool.0167M potassium dichromate. no precipitate is produced. C. dilute to 100 ml with water and filter. Boil 0. Melting point.

Appendix II B. PARACETAMOL TABLETS PARACETAMOL TABLETS BP 500 MG FPS/PARA-500/01 01/01/2004 SUPERSEDES : --PAGE NO. Contact :: info@icpc.1M sodium hydroxide in the reference cell. C8H9NO2. Use as the medium 900 ml of phosphate buffer pH 5.1M sodium hydroxide to give a solution expected to contain about 0. Calculate the total content of paracetamol. Appendix XII D.biz 114 Website :: http://icpc.aspx . : : : : : : FINISHED PRODUCT METHOD OF ANALYSIS. Dilute the filtrate with 0. in the medium taking 715 as the value of A(1%. In the chromatogram obtained with solution (2) peaks with a long retention time may occur due to excipients (0.8 and rotate the paddle at 50 revolutions per minute. QUALITY CONTROL. using Apparatus II.biz/PharmaceuticalDossier. 1 cm) at the maximum at 257 nm.1%) 6. Measure the absorbance of this solution.XYZ PHARMACEUTICAL SUBJECT DEPARTMENT PRODUCT NAME GENERIC NAME FPS NO. Withdraw a sample of 20 ml of the medium and filter. : 03 / 05 EFFECTIVE DATE In the chromatogram obtained with solution (2) the area of any peak corresponding to 4aminophenol is not greater than the area of the peak in the chromatogram obtained with solution (1). at the maximum at 257 nm using 0.00075% w/v of Paracetamol. Dissolution : Comply with the dissolution test for tablets and capsules.

: 04 / 05 EFFECTIVE DATE 7. For solution (4) dissolve 0.0050% w/v of 4´-chloroacetanilide in ethanol (96%). After removal of the plate. shake mechanically for 30 minutes. add 5 ml of peroxide-free ether.10 g of paracetamol in sufficient ethanol (96%) to produce 100 ml. For solution (1) transfer a quantity of the finelypowdered tablets containing 1. using silica gel GF254 as the coating substance and a mixture of 10 volumes of toluene. dry it in a current of warm air and examine under ultraviolet light (254 nm). Apply separately to the plate 200 µl of solution (1) and 40 µl of each of solutions (2).25 g of 4´-chloroacetanilide and 0.biz 115 Website :: http://icpc. : : : : : : FINISHED PRODUCT METHOD OF ANALYSIS. centrifuge at 1000 revolutions per minute for 15 minutes or until a clear supernatant liquid is obtained and use the supernatant liquid. Appendix III A. QUALITY CONTROL.aspx .XYZ PHARMACEUTICAL SUBJECT DEPARTMENT PRODUCT NAME GENERIC NAME FPS NO. Solution (3) contains 0. For solution (2) dilute 1 ml of solution (1) to 10 ml with ethanol (96%). 25 volumes of acetone and 65 volumes of chloroform as the mobile phase.0 g of Paracetamol to a ground-glass-stoppered 15 ml centrifuge tube. PARACETAMOL TABLETS PARACETAMOL TABLETS BP 500 MG FPS/PARA-500/01 01/01/2004 SUPERSEDES : --PAGE NO.biz/PharmaceuticalDossier. Related Substance: Carry out the method for thin-layer chromatography. close the tank and allow the solvent front to ascend 14 cm above the line of application. Pour the mobile phase into an unlined tank. (3) and (4). Any spot corresponding to 4´-chloroacetanilide in the chromatogram obtained with solution (1) is not more intense than the spot in the chromatogram obtained with solution (3). Any secondary spot in the Contact :: info@icpc. immediately place the prepared plate in the tank.

1 cm) at the maximum at 257 nm. the spot corresponding to 4´-chloroacetanilide having the higher Rf value. dilute to 100 ml with water and measure the absorbance of the resulting solution at the maximum at 257 nm. Add a quantity of the powder containing 0. Mix. 8.15 g of Paracetamol to 50 ml of 0. : : : : : : FINISHED PRODUCT METHOD OF ANALYSIS. QUALITY CONTROL. Contact :: info@icpc. Add 10 ml of the resulting solution to 10 ml of 0. filter and dilute 10 ml of the filtrate to 100 ml with water.XYZ PHARMACEUTICAL SUBJECT DEPARTMENT PRODUCT NAME GENERIC NAME FPS NO.1M sodium hydroxide. shake for 15 minutes and add sufficient water to produce 200 ml. Calculate the content of C8H9NO2 taking 715 as the value of A(1%. PARACETAMOL TABLETS PARACETAMOL TABLETS BP 500 MG FPS/PARA-500/01 01/01/2004 SUPERSEDES : --PAGE NO. The test is not valid unless the chromatogram obtained with solution (4) shows two clearly separated principal spots. Appendix II B. dilute with 100 ml of water.biz 116 Website :: http://icpc.Assay : Weigh and powder 20 tablets.aspx . : 05 / 05 EFFECTIVE DATE chromatogram obtained with solution (2) with an Rf value lower than that of 4´chloroacetanilide is not more intense than the spot in the chromatogram obtained with solution (3).1M sodium hydroxide.biz/PharmaceuticalDossier.

aspx Contact :: info@icpc. 17 Mg. 11 Mg. 02 Mg 07 Mg . % 15 Mg.5 / 10 % 117 Website :: http://icpc. Wt. 20 Mg. 18 Mg. of 20 Tablets Av. Paracetamol Tablet BP White colour round uncoated Tablet. 03 Mg 08 Mg . 16 Mg. Gms. Pharmacopial Limit : ± 4 / 5 / 7. of Tablet Desintegration Time Diameter / Length Thickness Width Friability Hardness Uniformity of weight Mg 06 Mg .XYZ PHARMACEUTICAL QUALITY CONTROL DEPARTMENT TABLET PHYSICAL TEST REPORT 01 02 03 04 05 06 07 08 09 10 11 12 01 Batch No.biz . Range Mg. 05 Mg 10 Mg . Gm. Name of Product Description Wt. 14 Mg. 13 Mg. 04 Mg 09 Mg . % Heigher Wt. To Mg. 19 Mg. Mins mm Mm mm % Kg/Cm² mm Secs. Lower Wt. 12 Mg.biz/PharmaceuticalDossier.

biz/PharmaceuticalDossier.biz 118 Website :: http://icpc.S. (tablets) BP'2005 Effective Date NA Review Date NA Page No./U. contents of twenty units. Approved By: Name of Test Reference Reason for revision Supersedes : : : : : : 01/01/07 : 01/12/08 : 1 of 1 Weigh individually twenty units taken at random or.XYZ PHARMACEUTICAL Uniformity of wt.P. and determine the average weight (mass). Contact :: info@icpc./ In-House Date : QUALITY ASSURANCE DEPARTMENT STANDARD OPERATING PROCEDURE Uniformity of Weight SOP No. Standards Analyst : : Complies / Does Not Complies as per I.aspx . for single-dose preparations presented in individual containers./B. Not more than two of the individual weights (masses) deviate from the average weight (mass) by more than the percentage deviation shown in Table 12G-1 and none deviates by more than twice that percentage.P.P.

biz/PharmaceuticalDossier. One side of the drum is removable. Apparatus Use a drum with an internal diameter between 283 and 291 mm and a depth between 36 mm and 40 mm. Tablets BP'2005 Effective Date NA Review Date NA Page No. 17G-1).5 mm and 85.biz 119 Website :: http://icpc. made of a transparent synthetic polymer with polished internal surfaces and not subject to static build-up (see Fig. Thus. The tablets are tumbled at each turn of the drum by a curved projection with an inside radius between 75.XYZ PHARMACEUTICAL CHEMIST QA/QC IN CHARGE MANAGER Approved by Prepared by Checked by Name of Test Reference Reason for revision Supersedes : : : : QUALITY ASSURANCE DEPARTMENT STANDARD OPERATING PROCEDURE Friability of Uncoated SOP No. the friability of uncoated tablets. : QC/SOP/109 : 01/12/05 : 01/12/06 : 1 of 2 This test is intended to determine. at each turn the tablets roll or slide and fall onto the drum wall or onto each other.aspx . The drum is attached to the horizontal axis of a device that rotates at 25 ± 1 r/m.5 mm that extends from the middle of the drum to the outer wall. under defined conditions. the phenomenon whereby tablet surfaces are damaged and/or show evidence of lamination or breakage when subjected to mechanical shock or attrition. Contact :: info@icpc.

XYZ PHARMACEUTICAL

Fig. 17G-1 Tablet friability apparatus Dimensions in mm

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XYZ PHARMACEUTICAL

Name of Test Reference Reason for revision Supersedes Method

: : : :

QUALITY ASSURANCE DEPARTMENT STANDARD OPERATING PROCEDURE Friability of Uncoated SOP No. Tablets BP'2005 Effective Date NA Review Date NA Page No.

: QC/SOP/109 : 01/12/05 : 01/12/06 : 2 of 2

For tablets weighing up to 0.65 g each, take a sample of twenty tablets; for tablets weighing more than 0.65 g each, take ten tablets. Place the tablets on a sieve no. 1000 and remove any loose dust with the aid of air pressure or a soft brush. Accurately weigh the tablet sample and place the tablets in the drum. Rotate the drum 100 times and remove the tablets. Remove any loose dust from the tablets as before. If no tablets are cracked, split or broken, weigh the tablets to the nearest milligram. Generally the test is run once. If the results are doubtful or if the mass loss is greater than 1%, repeat the test twice and determine the mean of the three tests. A maximum loss of 1% of the mass of the tablets tested is considered to be acceptable for most products.

For tablets having a diameter of 13 mm or greater, problems of reproducibility may be encountered due to

frequent irregular tumbling. In such cases, adjust the drum so that the tablets may fall freely and do not bind together when lying next to each other, adjusting the drum so that the axis forms a 10° angle with the base is usually satisfactory. Expression of the results The friability is expressed as the loss of mass and it is calculated as a percentage of the initial mass.
Contact :: info@icpc.biz 121 Website :: http://icpc.biz/PharmaceuticalDossier.aspx

XYZ PHARMACEUTICAL

Indicate the number of tablets used.

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QUALITY ASSURANCE DEPARTMENT STANDARD OPERATING PROCEDURE Name of Test Reference Reason for revision Supersedes 1 2 3 4 5 6 7 : : : : Description In-House NA NA SOP No. Effective Date Review Date Page No. : : : : QC/SOP/115 01/12/01 01/12/02 1 of 1

Observe the sample immediately after receipt. Observe the sample on the piece of paper under sufficient light. Observe the sample of black and white particles and foreign matters. Observe the sample for colour and odor. Observe the sample for clarity for liquid samples. Record your observations in the worksheet. Inform your immediate supervisor in case of any abnormal observation.

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Add a disc to each tube. repeat the test on a further six tablets omitting the discs. 12A1).biz 124 Website :: http://icpc. 21.0 to 80. and examine the state of the tablets. b.9. Use water R as the liquid medium.5 mm in internal diameter and with a wall thickness of about 2 mm (see Fig.aspx .XYZ PHARMACEUTICAL Disintegration Time (Ref: BP). A rigid basket-rack assembly supporting six cylindrical glass tubes 75. Operate the apparatus for 15 min.0 mm long. Disintegration Uncoated tablets comply with the test for disintegration of tablets and capsules (2. The tablets comply with the test if all six have disintegrated.1).biz/PharmaceuticalDossier. unless otherwise justified and authorised. Apparatus a. If the tablets fail to comply because of adherence to the discs. Contact :: info@icpc.

aspx . one Contact :: info@icpc. pierced with five holes.biz/PharmaceuticalDossier. made of transparent plastic with a relative density of 1.35 to 9. each 20.85 mm in diameter and 9.XYZ PHARMACEUTICAL Fig.20. each 2 mm in diameter. 12A-1 Apparatus for the Disintegration of Tablets and Capsules Dimensions in mm (b) A cylindrical disc for each tube.55 to 20.18 to 1.65 mm thick.biz 125 Website :: http://icpc.

The design of the basket-rack assembly may be varied provided that the specifications for the glass tubes and 126 Website :: http://icpc. Four equally-spaced grooves are cut in the lateral surface of the disc in such a way that at the upper surface of the disc they are 9.6 mm square. perforated by six holes.5 mm wide and 2. The volume of liquid is such that when the assembly is in the highest position the wire mesh is at least 15 mm below the surface of the liquid and when the assembly is in the lowest position the wire mesh is at least 25 mm above the bottom of the beaker and the upper open ends of the tubes remain above the surface of the liquid.biz . (d) The plates are held rigidly in position and 77. (f) A suitable device maintains the temperature of the liquid at 36° to 38°. Attached to the under side of the lower plate is a piece of woven gauze made from stainless steel wire 0.55 mm deep and at the lower surface 1.XYZ PHARMACEUTICAL in the centre and the other four spaced equally on a circle of radius 6 mm from the centre of the disc. (c) The tubes are held vertically by two superimposed transparent plastic plates 90 mm in diameter and 6 mm thick. preferably a 1000-ml beaker.biz/PharmaceuticalDossier.00 mm.635 mm in diameter and having nominal mesh apertures of 2. The holes are equidistant from the centre of the plate and are equally spaced from one another.aspx Contact :: info@icpc. (e) The assembly is suspended in the specified liquid medium in a suitable vessel.5 mm apart by vertical metal rods at the periphery and a metal rod is also fixed to the centre of the upper plate to enable the assembly to be attached to a mechanical device capable of raising and lowering it smoothly through a distance of 50 to 60 mm at a constant frequency of between 28 and 32 cycles per minute.

XYZ PHARMACEUTICAL wire mesh are maintained. Remove the assembly from the liquid. introduce one tablet or capsule into each tube and. The tablets or capsules pass the test if all six have disintegrated.biz 127 Website :: http://icpc. Method Unless otherwise stated in the individual monograph. add a disc to each tube. Suspend the assembly in the beaker containing the specified liquid and operate the apparatus for the specified time. if prescribed in the appropriate general monograph.biz/PharmaceuticalDossier. Contact :: info@icpc.aspx .

type 316 or equivalent or coated with a suitable material to ensure that such parts do not react or interfere with the preparation being examined or the dissolution medium. react or interfere with the preparation being examined. All metal parts of the apparatus that may come into contact with the preparation or the dissolution medium must be made from stainless steel.XYZ PHARMACEUTICAL DISSOLUTION TEST FOR TABLETS AND CAPSULES (As per BP’2002) Use Apparatus 1 unless otherwise directed. Contact :: info@icpc.aspx . All parts of the apparatus that may come into contact with the preparation being examined or with the dissolution medium are chemically inert and do not adsorb.biz 128 Website :: http://icpc.biz/PharmaceuticalDossier.

7. agitation or vibration beyond that due to the smoothly rotating element. Apparatus 1 An assembly consisting of the following: A cylindrical vessel.The vessel has a flanged upper rim and is fitted with a lid that has a number of openings. contributes significant motion. with a hemispherical bottom and with a nominal capacity of 1000ml.biz/PharmaceuticalDossier. An apparatus that permits observation of the preparation being examined and the stirrer during the test is preferable. B (see Fig. A motor with a speed regulator capable of maintaining the speed of rotation of the paddle within 4% of that specified in the individual monograph.3. including the environment in which the assembly is placed. The motor is fitted with a stirring element which consists of a drive shaft and blade forming a paddle.biz . made of borosilicate glass or any other suitable transparent material. A.2) 129 Website :: http://icpc.aspx Contact :: info@icpc. one of which is central.XYZ PHARMACEUTICAL No part of the assembly.

XYZ PHARMACEUTICAL The blade passes through the diameter of the shaft so that the bottom of the blade is flush with the bottom of the shaft. When Apparatus 1 is used. into the vessel of the apparatus. the test may be concluded in a shorter period if the requirement for the minimum amount dissolved is met. or at each of the times stated. When Apparatus 2 is used. specimen are to be withdrawn only at the stated times. Warm the dissolution medium to between 36. Contact :: info@icpc. Method: Introduce the stated volume of the dissolution medium.biz 130 Website :: http://icpc.05 units of the pH specified in the monograph. free from dissolved air.5° and 37. place the tablet or capsule in a dry basket at the beginning of each test. is minimised Dissolution medium: Use the dissolution medium specified in the individual monograph. Care should be taken to ensure that air bubbles are excluded from the surface of the tablet or capsule. If the medium is a buffered solution. A suitable device such as a wire of glass helix may be used to keep horizontal at the bottom of the vessel tablets or capsules that would otherwise float. add a volume of dissolution medium equal to the volume of the samples withdrawn. Where two or more tablets or capsules are directed to be placed together in the apparatus. adjust the solution so that its pH is within 0. Unless otherwise stated use one tablet or capsule.5° . Lower the basket into position before rotation.aspx . A water -bath set to maintain the dissolution medium at 36. The bath liquid is kept in constant and smooth motion during the test. Within the time interval specified. The shaft is positioned so that its axis is within 2 mm of the axis of the vessels and the lower edge of the blade is 23 to 27 mm from the inside bottom of the vessel. within a tolerance of ± 2%. If two or more times are specified. not less than 10mm from the wall of the vessel.5° . The dissolution medium should be deaerated prior to testing. The apparatus operates in such a way that the paddle rotates smoothly and without significant wobble. withdraw a specimen from a zone midway between the surface of the dissolution medium and the top of the rotating blade or basket.biz/PharmaceuticalDossier. Perform the analysis as directed in the individual monograph. Operate the apparatus immediately at the speed of rotation specified in the individual monograph. Except in the case of single sampling.5° to 37. including the water circulation device. carry out six replicate tests. Repeat the whole operation five times. Time: Where a single time specification is given in the monograph. The vessel is securely clamped in the water-bath in such a way that the displacement vibration from other equipment. allow the tablet or capsule to sink to the bottom of the vessel prior to the rotation of the paddle.

and dissolve the empty capsule shells in the specified volume of the dissolution medium.biz/PharmaceuticalDossier. continue testing with additional tablets or capsules through stages S2 and S3 unless the result conform at stage S2.aspx .15% and no unit is less than D . Contact :: info@icpc. Where capsule shells interfere with the analysis. Perform the analysis as directed in the individual monograph.25% *D is the amount of dissolved active ingredient specified in the individual monograph.Acceptance Table Stage S1 Number Tested 6 Acceptance Each unit is not less than D* + 5% S2 6 Average of 12 units (S1 +S2) is equal to or greater than D. remove the contents of not less than 6 capsules as completely as possible. Make any necessary correction. determine for each test the amount of active ingredient in solution per tablet or capsules and calculate as a percentage of the stated amount. TABLE 1.XYZ PHARMACEUTICAL For each of the tablet or capsule tested. not. expressed as a percentage of the stated amount. If the results do not conform to the requirements at stage S1 given in the accompanying acceptance table (Table 1). Is equal t or greater than D. More than 2 units are less than D . S3 12 Average of 24 units (S1+S2+S3).biz 131 Website :: http://icpc. Correction factors should not be greater than 25% of the stated amount. and no unit is less than D 15%. calculate the amount of dissolved active ingredient in solution as a percentage of the stated amount where two or more tablets or capsules are placed together.

biz/PharmaceuticalDossier.biz 132 Website :: http://icpc.XYZ PHARMACEUTICAL PART II F STABILITY TESTS ON THE FINISHED PRODUCT Contact :: info@icpc.aspx .

0 % Min. round. DATE PACK STYLE : : Aug’2007 10X10TABLETS IN BLISTER Months Description Disintegration Time NMT 15 Mins.biz/PharmaceuticalDossier.: 90.aspx 131 . White Round.S. uncoated tablet. 07 Mins.0 – 105. 30 Secs.31 % 98. Un coated tablet. 06 Mins. 06 Mins.30 % Min. Temperature 40°C ±2. 07 Mins.: 88. White Round. BATCH NO MFG.24 % 99.29 % Initial 01 02 03 06 White Round. Uncoated tablet.Uncoated tablet.: 85. 500mg.: 92. DATE : : R400227 Sep’2004 CONDITION DESCRIPTION : : EXP. EXCIPIENTS…………………Q.34 % Min.35 % Min. 07 Mins.Uncoated tablet. 40 Secs.0°C Humidity : 75%. 51 Secs.56 % 98. White Round. Dissolution NLT 75.A. INCHARGE Contact :: info@icpc. 11 Secs.37 % 100. White Round.04 % Analysed By Remarks Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification CONCLUSION: From the data observed in above table are carried out as per In-House Specification & it is evident that the Product is within permissible limit.0 % 100. 24 Secs.XYZ PHARMACEUTICAL ACCELERATED STABILITY PROTOCOL PRODUCT NAME LABEL CLAIM : : PARACETAMOL TABLET BP 500 MG Each Uncoated tablet ontains: PARACETAMOL BP……….0 % white. Uncoated tablet. ±5. Assay 95. CHECKED BY Q.: 89.31 % Min.biz Website :: http://icpc.

tablet.: 94.03 % Min.33 % 97.biz Website :: http://icpc. White. ±5.0°C Humidity : 75%.biz/PharmaceuticalDossier.45 % Min.: 92. 07 Mins. tablet.40 % Initial 01 02 03 06 White. Uncoated round. 07 Mins.35 % Min. Uncoated Assay 95. White. 08 Mins. EXCIPIENTS……………….20 % Min.67 % 100. CHECKED BY Q. DATE PACK STYLE : : Oct’2007 10X10TABLETS IN BLISTER Months Description Disintegration Time NMT 15 Mins.aspx 132 . INCHARGE Contact :: info@icpc.Q.XYZ PHARMACEUTICAL ACCELERATED STABILITY PROTOCOL PRODUCT NAME LABEL CLAIM : : PARACETAMOL TABLET BP 500 MG Each Uncoated tablet contains: PARACETAMOL BP……. Dissolution NLT 75. round. White. BATCH NO MFG. 42 Secs. 08 Mins. 49 Secs. Uncoated Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification CONCLUSION: From the data observed in above table are carried out as per In-House Specification & it is evident that the Product is within permissible limit.39 % 98.51 % 99. Uncoated tablet. Uncoated round. Temperature 40°C ±2.: 92. tablet. Uncoated round.0 % Min.: 90. DATE : : R400228 Nov’2004 CONDITION DESCRIPTION : : EXP.0 % White round.A. tablet. 22 Secs.0 % 100. White tablet.. 08 Mins.: 93. 34 Secs. 12 Secs. 500mg.0 – 105.03 % Analysed By Remarks round.S.

16 % Min. White. DATE : : R400229 Dec’2004 CONDITION DESCRIPTION : : EXP. Dissolution NLT 75. Uncoated round.0 % Min. INCHARGE Contact :: info@icpc. round.biz/PharmaceuticalDossier. BATCH NO MFG.32 % Min.: 84. 500 mg. tablet. White. 22 Secs.36 % Initial 01 02 03 06 White tablet.0°C Humidity : 75%. 03 Secs.21 % 99. Uncoated Assay 95.biz Website :: http://icpc.aspx 133 .: 85. Uncoated round.33 % Min. EXCIPIENTS…………………Q.36 % Min. 09 Mins.0 % 100. UNcoated Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification Sample complies as per InHouse Specification CONCLUSION: From the data observed in above table are carried out as per In-House Specification & it is evident that the Product is within permissible limit. 12 Secs. Uncoated tablet. White. Temperature 40°C ±2.0 – 105.: 92.: 88.21 % 98.0 % White. CHECKED BY Q.A. 23 Secs. 07 Mins. 46 Secs.35 % 98.03 % 97.: 90. 07 Mins. tablet.XYZ PHARMACEUTICAL ACCELERATED STABILITY PROTOCOL PRODUCT NAME LABEL CLAIM : : PARACETAMOL TABLET BP 500MG Each Uncoated tablet contains: PARACETAMOL BP………. 08 Mins.22 % Analysed By Remarks round. White.S. round. ±5. Uncoated round. tablet. tablet. 07 Mins. DATE PACK STYLE : : Nov’2007 10X10TABLETS IN BLISTER Months Description Disintegration Time NMT 15 Mins.

: 93. ±5.0 % Min.36 % Min. DATE : : R400227 Sep’2004 EXP. tablet. round. White tablet.A. DATE : : Aug’2007 Description round. round. 07 Mins.: 92.35 % Min. 08 Mins. 22 Secs. Un coated tablet.0 % White .XYZ PHARMACEUTICAL PRODUCT NAME LABEL CLAIM : : CONDITION DESCRIPTION Months Initial 06 12 18 24 36 White. 08 Mins.35 % Min. 51 Secs. 08 Mins.biz/PharmaceuticalDossier. tablet.84 % 97. tablet. INCHARGE Contact :: info@icpc. 06 Mins.Q.0 % 100.03 % 97. Temperature 30°C ±2. tablet. CHECKED BY Q.biz Website :: http://icpc.85 % Min. 06 Mins. White.S.0 – 105. Un coated Un coated Un coated Un coated Un coated Un coated Disintegration Time NMT 15 Mins. round.51 % 99. 34 Secs. 40 Secs.16 % Assay 95.0°C Humidity : 40%. White. round. BATCH NO MFG. 22 Secs. round.34 % 97.: 90.: 84. Dissolution NLT 75. round.aspx 134 .37 % 99.24 % PACK STYLE Analysed By 10X10 TABLETS IN BLISTER Remarks Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification CONCLUSION: From the data observed in above table are carried out as per In-House Specification & it is evident that the Product is within permissible limit.34 % Min. White.: 85.: 88. White tablet. 46 Secs. : : REAL TIME STABLITY PROTOCOL PARACETAMOL TABLET BP 500MG Each Uncoated tablet contains: PARACETAMOL BP ………500mg. EXCIPIENTS……………….

08 Mins. Un coated round.: 90. White tablet. tablet.S. 34 Secs. Temperature 30°C ±2.06 % 95. Uncoated Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification CONCLUSION: From the data observed in above table are carried out as per In-House Specification & it is evident that the Product is within permissible limit.: 89.: 85. White.Q. tablet. Dissolution NLT 75. CHECKED BY Q. Un coated tablet. ±5. tablet.A. 09 Mins.36 % Min. 09 Mins. 21 Secs.XYZ PHARMACEUTICAL PRODUCT NAME LABEL CLAIM : : CONDITION DESCRIPTION Months : : REAL TIME STABLITY PROTOCOL PARACETAMOL TABLET BP 500MG Each Uncoated tablet contains: PARACETAMOL BP………. DATE : : Oct’2007 Description Disintegration Time NMT 15 Mins. INCHARGE Contact :: info@icpc.03 % Min.03 % Min. DATE : : R400228 Nov’2004 EXP. round..biz/PharmaceuticalDossier.19 % 95.06 % PACK STYLE Analysed By 10X10TABLETS IN BLISTER Remarks round.biz Website :: http://icpc.67 % 98. 12 Secs. 54 Secs. 500 mg.: 84. White. 08 Mins.aspx 135 .89 % Initial 06 12 18 24 36 White. EXCIPIENTS………………. Un coated round. tablet. Un coated round.0 % Min. 09 Mins. White. round.0°C Humidity : 40%.: 92.0 % White.49 % Min.06 % 96. White. 07 Mins. Uncoated Assay 95.0 – 105. 12 Secs. BATCH NO MFG. 20 Secs.35 % 97. tablet. Un coated round.0 % 100.20 % Min.: 94.

34 % Min.36 % 98. CHECKED BY Q. 24 Secs. round.0 – 105.: 92. 07 Mins. White. INCHARGE Contact :: info@icpc. 09 Mins.32 % Min. BATCH NO MFG. Disintegration Time NMT 15 Mins.: 82. ±5. 08 Mins. 03 Secs.XYZ PHARMACEUTICAL REAL TIME STABLITY PROTOCOL PRODUCT NAME LABEL CLAIM : : PARACETAMOL TABLET BP 500MG Each Uncoated tablet contains: PARACETAMOL BP………. DATE : : R400229 Dec’2004 CONDITION DESCRIPTION : : EXP. round. Un coated tablet White. round..aspx 136 . Un coated tablet. round. Pink.06 % Analysed By Remarks Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification Sample complies as per In-House Specification CONCLUSION: From the data observed in above table are carried out as per In-House Specification & it is evident that the Product is within permissible limit.: 86.21 % 100.54 % 100. round.03 % 99. Un coated tablet.05 % 98.06 % Min. DATE PACK STYLE : : Nov’2007 10X10TABLETS IN BLISTER Months Initial 06 12 18 24 36 Description White.A.0 % Min. 09 Mins.S Temperature 30°C ±2. White. EXCIPIENTS…………………Q.: 78. Un coated tablet. 09 Mins. White.0 % White.34 % Min. 23 Secs. 40 Secs. Dissolution NLT 75.biz Website :: http://icpc. Un coated tablet. 500mg.0 % 100. 10 Secs. round.: 80.36 % Assay 95.biz/PharmaceuticalDossier. 09 Mins.: 90. Film coated tablet. round.36 % Min.0°C Humidity : 40%. biconvex. 34 Secs. Un coated tablet.

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