S. No. 1. 2. 3. 4. 5. 6. 7. 8. 9. 10. 11. 12. 13. 14. 15. 16. 17. 18. 19. 20. 21. 22. 23. 24. 25. 26. 27. 28. 29. 30. 31. 32. 33. 34. 35. 36. 37. 38. 39. 40. 41. 42. 43. 44. 45. 46. 47. 48.

Index Topic Weight Variation Solubility Composition of simulated gastric / intestinal fluid Informative Web sites Empty Hard Gelatin Capsules Physical Specification Weight Of Empty Hard Gelatin Capsules Stability Conditions Die - Punch Tooling Specification (Euro) pH of Human Organs Differential Scanning Calorimetry (DSC) Differential Thermal Analysis (DTA) Thermogravimetric Analysis (TGA) Compatibility Study and Excipients Selection Density of solvents API: Excipients compatibility study (Stress Testing) Solvent Classification BCS Classification RSD PARA I, II, III, IV. f2 Calculation (Similarity factor) Dissolution Apparatus as per USP Types of Drug Master Files SIF & SGF Tip speed Calculation Ideal Property of API for Tableting Weight variation Hardness Friability Thickness Disintegration Coating machine Glass standards (USP) Tap Density apparatus (USP) Equilibrium Relative Humidity or the ERH Capsule (USP) Powder flow Injection Recommended excess volume to be added (USP) STANDARD MESH SIEVE SIZES Stability Testing (Climatic Zone, Evaluation) Significance change (In stability testing) Photo stability - Light source: WHAT IS SUPAC GUIDANCE? Types of Tablets Tablet excipient SUSPENSION INGRIDIENTS Parameters used in IVIVC Zeta potential EMULSION INGRIDIENTS

1. Weight Variation Weight variation of tablets (Uncoated, film coated, coated tablet other than film coated) Avg weight of the tablet, mg IP Percentage difference 80 or less 10 More than 80 but less than 250 7.5 250 or more 5 80 or less 10 More than 80 but less than 250 7.5 250 or more 5 Capsule and granules (uncoated, single dose and powder, single dose) Less than 300 mg 10 300 mg or more 7.5 Powders for parenteral use More than 40 mg 10 Suppositories and pessaries All mass 5 130 or less 10 From 130 through 324 7.5 More than 324 5 Avg weight of the tablet,mg Percentage difference 80 or less 10 More than 80 but less than 250 7.5 250 or more 5 Capsule and granules (uncoated, single dose and powder, single dose) Less than 300 mg 10 300 mg or more 7.5 Powders for parenteral use More than 40 mg 10 Suppositories and pessaries All mass 5 References 1996 edition, vol2, page-736 2005 edition, vol4, page-A 291

BP

USP

USP-28, page2781 EP -5.0,vol-1, page-233

2. Solubility Solubility profile (USP) Descriptive form Very soluble Freely soluble Soluble Sparingly soluble Slightly soluble Very slightly soluble Practically insoluble

JP

Parts of solvent required for 1 Parts of solute Less than 1 From 1 to 10 From 10 to 30 From 30 to 100 From 100 ml to 1000 From 1000 to 10,000 10,000 Over

3. Composition of simulated gastric / intestinal fluid Sl. No. 1 2 3 4 5 Composition of simulated gastric fluid Sodium chloride Purified pepsin HCl Water Composition of simulated intestinal fluid Monobasic potassium phosphate. Sodium hydroxide. Water. Pancreatin. NaOH or HCl (pH 6.8±0.1).

4. Informative Web sites Sl.no. Web sites Purpose 1. vidal.fr Composition of innovators 2. luhs.com Image and information of innovator 3. tsrlinc.com/search3.cfm BCS classification 4. drugs.com Information of drug 5. rxlist.com Innovator and its information 6. Answers.com Answer 7. Drugsearcher.com 8. Sengpielaudio.com/convForce.htm Conversion of units 9. Emc.medicines.org.uk/ About API 10. Dissolution.com(By-law) Sending mail for disso problems 11. Fda.gov/cder/ogd/ 12. Pharmacopoeia.cn/usp.asp 13. google.com 14. Orange book Innovators 15. Uspto---homepage---patent--search I)issued patent---QS 2)published patent---Q.S 16. europianpatent---homepage--@spanet homepage---AS 17. Cder---freedom of information--index---cder---search 18. Drugbank---homepage 19. www.aapspharmsci.org Literatures 20. Pat2pdf Full Patent Pdf Books references 21. Merk Index 22. Martindale 23. PDR 24. Medicine Compendium 25. Therapeutic Drugs 26. British Pharmacopoeial Codex 27. Florey 28. USP 29. Ph EP 30. BP 31. JP 32. CP 33. Niazi

5. Empty Hard Gelatin Capsules Physical Specification Size 000 00 0 1 2 3 4 5 Outer Diameter (mm) 9.91 8.53 7.65 6.91 6.35 5.82 5.31 4.91 Height/ Lock length (mm) 26.14 23.30 21.70 19.40 18.00 15.90 14.30 11.10 Actual volume (ml) 1.37 0.95 0.68 0.50 0.37 0.30 0.21 0.13 Typical fill weight (mg) 0.7 powder density 960 665 475 350 260 210 145 90

6. Weight Of Empty Hard Gelatin Capsules Size 0 1 2 3 4 7. Stability Conditions Storage Condition At room temperature Study Long term Condition 250C±20C/60±5%RH 300C±20C/65±5%RH 300C±20C/75±5%RH 400C±20C/75±5%RH 50C±30C 250C±20C/60±5%RH -200C±50C Period (month) 12 6 6 12 6 12 Testing Frequency in (month) 0, 3, 6, 9 & 12 0, 3 & 6 0, 3 & 6 0, 3, 6, 9 & 12 0, 3 & 6 0, 3, 6, 9 & 12 Weight in mg 96 76 63 50 40

Intermediate Accelerated In refrigerator Long term Accelerated In freezer Long term

8. Die - Punch Tooling Specification (Euro) PUNCH Punch TOOLING Diameter (mm) 19.05 BB 19.05 B 25.4 BD 25.4 D Die Diameter (mm) 24 30.16 30.16 38.1 Max Tab Size Round Tablet Shaped Tablet (mm) (mm) 13 14 16 19 19 19 25 25

This differential temperature is then plotted against time. such as glass transitions. By observing the difference in heat flow between the sample and reference. differential scanning calorimeters are able to measure the amount of heat absorbed or released during such transitions. For example. while recording any temperature difference between sample and reference. Generally. Both the sample and reference are maintained at nearly the same temperature throughout the experiment. Likewise. Differential scanning calorimetry or DSC is a thermoanalytical technique in which the difference in the amount of heat required to increase the temperature of a sample and reference are measured as a function of temperature. DTA is a thermoanalytic technique.9. the temperature program for a DSC analysis is designed such that the sample holder temperature increases linearly as a function of time. pH of Human Organs Organs Liver Stomach Large Intestine Small Intestine Colon pH 10. In DTA. Whether more or less heat must flow to the sample depends on whether the process is exothermic or endothermic. as the sample undergoes exothermic processes (such as crystallization) less heat is required to raise the sample temperature. more (or less) heat will need to flow to it than the reference to maintain both at the same temperature. as a solid sample melts to a liquid it will require more heat flowing to the sample to increase its temperature at the same rate as the reference. the material under study and an inert reference are heated (or cooled) under identical conditions. when the sample undergoes a physical transformation such as phase transitions. or against temperature DTA curve or thermogram. similar to differential scanning calorimetry. This is due to the absorption of heat by the sample as it undergoes the endothermic phase transition from solid to liquid. DSC is widely used in industrial settings as a quality control instrument due to its applicability in evaluating sample purity and for studying polymer curing 11. The basic principle underlying this technique is that. DSC may also be used to observe more subtle phase changes. The reference sample should have a well-defined heat capacity over the range of temperatures to be scanned. .

1:5 1:0. Compatibility Study and Excipients Selection Plan for Study 1. 13.05 15. A derivative weight loss curve can be used to tell the point at which weight loss is most apparent.5 1:0. and temperature change. the weight loss curve may require transformation before results may be interpreted. TGA is commonly employed in research and testing to determine characteristics of materials such as polymers. API + all excipients in proportion as in FPS.12. API < 5% w/w of target weight of FP API:Diluent API:Binder API:Disintegrant API:Lubricant API:Preservatives/ Colour 5%<API < 50% w/w of target weight of FP API > 50% w/w of target weight of FP 1:1 and 1:25 1:1 . It is also often used to estimate the corrosion kinetics in high temperature oxidation.5 1:0. and solvent residues.1 1:1 1:0. absorbed moisture content of materials. to determine degradation temperatures.2 1:0.790 0.5 1:0. interpretation is limited without further modifications and deconvolution of the overlapping peaks may be required. API alone 2. Such analysis relies on a high degree of precision in three measurements: weight.1 1:1 . Again. decomposition points of explosives. 4. 1:5 1:0.786 1. temperature. Density of Solvents Solvent Water IPA MDC Acetone Methanol Density (g/ml) 0.791 .997 0.325 0. API + API (for combined doses) 3.5 1:1 1:0. Thermogravimetric Analysis or TGA is a type of testing that is performed on samples to determine changes in weight in relation to change in temperature. API + individual excipients in proportion as in FPS. All excipients blend 5. As many weight loss curves look similar. the level of inorganic and organic components in materials. 1:5 1:5 1:1 .

05 M Fe2+ or Cu2+ 2-80C Concentration of API# API only Solid state API Time 15 Days 15 Days Evaluation parameter Visual & Chemical Visual & Chemical Chemical Chemical Chemical Visual & Chemical Visual & Chemical Acid Base Oxidation Solution stability Photolysis (Optional) 2:1 in 0.2 to 8.2 million lux.When testing degradability of APIs in combination.1 N HCL 2:1 in 0.hr florescent light and to near UV energy of not less than 200 watt hours/m2.14.0 1:1 with diluent 1-10 Days Metal ions (Optional) Control sample 1:1 with solution of metal ions Solid state API 1-10 days 15 Days Chemical If required # .1 N HCL 1:1 in 3% H2O2 1-10 Days 1-10 Days 1-3 hours 2% 4-24 hour solution/suspension over pH range of 1. the APIs should be in same ratio as in the FDC.1 N NaOH at 250C 3% H2O2 at 250C Rom temp. Metal halide.In each case. or UVB fluorescent lamp 0. Xe. API: Excipients compatibility study and Excipients selection API Forced degradation study: (Stress Testing) Stress factor Heat Humidity Conditions 600C 400C with 5% moisture in sealed glass vial 0. the diluent is either excipients or all excipients in the formulation in the same ratios as in the formulation. Hg. . . solution stability study at different pH Expose the test compound to 1.1 N HCL at 250C 0.

2-Dichloroethene 1.0 38. Carcinogen Toxic and environmental hazard 4 5 Toxic 8 Toxic 1500 Environmental hazard CLASS 2 SOLVENTS IN PHARMACEUTICAL PRODUCTS.8 CONCENTRATION LIMIT (PPM) 60 360 600 620 3000 3880 1870 80 410 100 1090 880 380 . Solvent Classification TABLE 1. CLASS 1 SOLVENT IN PHARMACEUTICAL PRODUCTS (SOLVENTS THAT SHOULD BE AVOIDED) SOLVENT CONCENTRATION LIMIT (PPM) 2 CONCERN Benzene Carbon tetrachloride 1.1.8 4.6 6.2 30.2-Dimethoxyethane N.4-Dioxane PDE (MG/DAY) 0.0 10.8 3.1.2-Trichloroethene Acetonitrile 1.9 8. SOLVENT Chloroform Chlorobenzene Dichloromethane (MDC) Ethylene Glycol Methanol Cyclo Hexane 1.1 1.7 0.NDimethylacetamide N.2Dichloroethane 1.1Trichloroethane TABLE 2.NDimethylformamide 1.6 3.16.0 6.8 18.1Dichloroethene 1.

0 1. 14% p-xylene.7 160 220 290 50 50 1180 4840 50 200 160 100 890 2170 usually 60% m-xylene. CLASS 3 SOLVENTS.9 0.5 11. 9% o-xylene with 17% ethyl benzene TABLE 3.6 1.5 0.9 21.0 8. Acetone (1500 ppm) 2-Propanol (IPA) Ethanol (1000 ppm) Anisole 1-Butanol 2-Butanol Butyl acetate tert-Butylmethyl ether Cumene Dimethyl sulfoxide Propyl acetate Ethyl acetate Ethyl ether Ethyl formate Acetic acid Isobutyl acetate Isopropyl acetate Methyl acetate 3-Methyl-1-butanol Methylethyl ketone Methylisobutyl ketone 2-Methyl-1-propanol Pentane 1-Pentanol 1-Propanol Tetrahydrofuran Formic acid (5000 ppm) Heptane .2-Ethoxyethanol Formamide Hexane 2-Methoxyethanol Methylbutyl ketone Methylcyclohexane N-Methylpyrrolidone Nitromethane Pyridine Sulfolane Tetralin Toluene Xylene* * 1. WHICH SHOULD BE LIMITED BY GMP OR OTHER QUALITYBASED REQUIREMENTS.2 2.4 0.8 48.5 2.6 2.

BCS Classification: Class I Class II Class III Class IV 18. Its value ranges from 0 – 100. Para IV .The patent for the drug has already expired Para III . III. IV • • • • Para I . Generally similarity value ranges from 50 – 100.The patent for the product exists but the generic company wants to enter the markets after the date of patent expiry passes. .Patent is not infringed upon or is invalid 20. II.100 means test and reference profiles are identical and 0 means the dissimilarity increases.The drug has not been patented Para II . f2 Calculation (Similarity factor) Logarithmic transformation of the sum of squares of the difference between test and reference profiles. PARA I.17. RSD Solubility High Low High Low Permeability High High Low Low 19.

21. and then adding water to 1000 ml. Apparatus 3 Reciprocating Cylinder Apparatus 4 Apparatus 5 Apparatus 6 Flow Through Cell Paddle Over Disc Rotating Cylinder Apparatus 7 Reciprocating Holder 22. and Material Used in Their Preparation. and then diluting with water to 1000 ml. Operating Procedures. SGF : As used herein. or Material Used in Their Preparation Type V: FDA Accepted Reference Information 23. Tip speed Calculation Tip speed= π nd 60x1000 ________________________________________________________ where n = rpm of impeller d = diameter of the impeller in mm) . and finally adding 0. SIF & SGF SIF: As used herein. `simulated gastric fluid` or `SGF` means a composition prepared by dissolving 2 g of NaCl and 3. The resulting fluid has a pH of about 1. Types of Drug Master Files Type I: Manufacturing Site. then adding 190 ml of 0. Dissolution Apparatus as per USP Apparatus 1 Apparatus 2 Basket Paddle Solid dosage form Solid dosage form Modified release solid dosage form Modified release solid dosage form with limited Solubility Transdermal Patches Transdermal Patches Non-disintegrating oral modified release oral dosage form and Transdermal Patches. Flavor. "simulated intestinal fluid" or "SIF" means a composition prepared by dissolving 6. 24.8 g of monobasic potassium phosphate in 250 ml of water.2 g pepsin in 7 ml of HCl.2 N NaOH. Colorant.5. 400 ml of water and 10 g of pancreatin. or Drug Product Type III: Packaging Material Type IV: Excipients.2. Facilities. Essence.2 N NaOH to adjust the pH to 7. Drug Substance Intermediate. and Personnel Type II: Drug Substance.

compressibility. dissolution. uniformity of weight. hydrolysis. It can be measured using angle of repose. Ideal Property of API for Tableting Property High purity High Stability Good compatibility with excipients Optimum bulk powder properties Reason Impurities can catalyze series of reaction should be stable against photolysis.Brittle fracture Remedy ------------------ Spherical shape Good flowability -Addition of glidants -Addition of fines -By wet granulation -By densification with help of slugging Optimum moisture content -Use of anhydrous salts. bioavailability.Elasticity 2. iii) Have good flow. The shape of particles decides flowability Flow is important for having uniformity of weight and uniformity of drug content. granule friability. -Use of non-aqueous solvent -Optimum drying time -Addition of finely powdered adsorbent like magnesium oxide Good compressibility . etc. -Moisture affects flow -High amount of moisture gives stickiness -Picking/sticking good compressibility depends upon its intrinsic nature like 1. drying rate kinetics of wet granulation. Optimum and Uniform particle size-particle size distribution It has pronounce effect on uniformity of content. stability. I) Prevent segregation. ii) Have optimum size tablet particularly for low potency-low density API. etc. flowability. oxidation. -Total lack of moisture results into brittle tablet. disintegration time.Plasticity 3.25. Carr’s index and Hausner ratio.

(mix liquid API with adsorbents) Valproic acid and Sodium Valproate is a typical example of converting a liquid into pseudosolid. addition of diluents or lubricant.Cyclodextrin approach. Requirements are met if not more than 2 tablets are outside % limit. wt.colour 2.BCS class IV drugs are difficult to formulate if dissolution and bioavailability requirements are to meet as per regulatory agencies. Apply coating Use small particle of colored API Taste. compare individual tablet weight with average weight. Coated tablets (other than film-coated): Weigh 20 tablets individually & calculate average weight. etc. wt of tablet (mg) Maximum % difference allowed 80 10 80-250 7.5 >250 5 .S. If the coated tablets do not conform to the criteria as given in table.5 >324 5 As per I.P. 26. surface coating with help of colloidal silica. Weight variation: Uncoated & Film coated tablets: Weigh 20 tablets individually & calculate average weight.P Avg. Weigh accurately 20 individual tablet cores & calculate the avg. Requirements are met if not more than 2 tablets are outside % limit. Compare individual tablet weight with average weight. Pro-drug approach Miscellaneous points -API should not exhibit sublime characteristics. Weight variation tolerances for uncoated. dry the cores at 500 for 30 min. .Liquid APIs are less suitable for tablet formulation. .Taste -For uniformity of dose and weight variation -It may cause segregation -Charged API may adhere to feed frame Ideally should be colorless Ideally should be Tasteless -Granulation. place 20 tablets in a beaker of water at 370 & swirl gently for not more than 5 min. Sweeteners. film coated & other than film coated tablets: As per U. Ion exchange absorbent. Avg.Absence of static charge on surface Good organoleptic properties 1. wt of tablet (mg) Maximum % difference allowed 130/less 10 130-324 7.

Requirements: 1. net content.807N 1Kg = 2. net content from sum of individual net wts. wt Requirement: Individual wt should be within limits of 90% & 110% of avg. Units: Kilogram (Kg) Newton (N) Pound (lb) 1Kg = 9. This method is used for research & development and for quality control. Also called tablet-crushing strength. It can also be useful for research & development . washing machine tablets. net content 2.Hardness: Force required to break a tablet in a compression test. content of entire 60 capsules. Remove contents of each capsule with emptied shell individually & calculate net wt of its content by subtracting wt of shell from sum of individual net wts. 3-point bend testing can be used for larger tablets i.Allow accluded solvent to evaporate from shells at room temperature over a period of about 30 min. Requirements: same as hard capsules. In no case difference is greater than 25% If more than 2 but not more than 6 capsules deviate from avg etween 1025% determine net contents of additional 40 capsules & determine avg. Not more than 2 of differences are greater than 90% of avg. Then determine difference between each individual net content & avg. Determine avg. The machine measures the force applied to the tablet and detects when it fractures.204ss lb Test Methods: The standard method used for tablet hardness testing is compression testing. Requirements: 1.Weigh individual shells& calculate net contents. If not all the capsules fall within given limits weigh 20 capsules individually. The tablet is placed between two jaws that crush the tablet.Hard gelatin capsules: Weigh 20 intact capsules individually & determine avg. net content 2. wt.e. In no case difference exceed 25% Soft capsules: Weigh 20 intact capsules individually to obtain their gross wts. Not more than 6 of 60 capsule’s differences exceed 10% of avg. 27. Cut open capsules & remove contents by washing wiyh a suitable solvent.

Youngs Modulus and tensile strength.inside radius: 80. Disintegration: Test is provided to determine whether tablets or capsules disintegrate within the prescribed time when placed in a liquid medium at the experimental conditions.5gm For tablets with unit wt >650mg = 10 tablets 29. 30.purposes to determine the mechanical properties of new formulations. Examples: Monsanto tester Strong-cobb tester Pfizer tester Erweka tester Schleuniger tester 28.g. Friability: Another measure of tablet’s strength E. remaining on the . e.take sample of whole tablet ~6.5m Curved projection. Thickness: Measured by vernier caliper Tablet thickness should be controlled within ±5% variation of a standard value.outer diameter: 25±0. except fragments of insoluble coating/capsule shell.g.5±5mm Loss in weight of tablets: not more than 1% For tablets with unit wt =/<650mg. Roche friabilator Standards: Drum: 283-291mm (ID) 36-40 mm (Depth) Drop height: 158±2mm RPM: 25±1 rpm Central ring. It is defined as that state in which any residue of the unit.

Thermostatic arrangement for heating liquid & maintaining temperature at 35±20C.such that at the highest point of upward stroke wire mesh remains at least 25mm (2.15mm(D) .7-23mm(D) 1.57-0.one in diameter & four spaced equally on circle of radius 6mm from the center of disc. Standards: Basket-Rack assembly: Beaker: capacity: 1000ml Dimensions: 138-160mm(H) 97-115mm (D) 6 open ended transparent tubes Dimensions: 77. Dimensions: 9.to move the basket at frequency = 28-32cycles/min through distance 53-57mm Volume of fluid.5cm) from the bottom of vessel on downward stoke.7±0.20 It consists of 5 holes each 2±0. Cylindrical disk.15mm(T) 20.5cm) below the surface of fluid & descends to not less than 25mm (2.5mm(L) 20.screen of test apparatus is a soft mass having no palpably firm core.2-8mm(T) 10 mesh (2mm) screen at the bottom of basket Wire diameter: 0.made up of suitable transparent plastic material having specific gravity between 1.1mm(D).5±0.66mm Standard motor driven device.18-1.5±2.

a) Coating Pan b) Air Blower c) Exhaust d) Spray Gun e) Peristaltic Pump f) Baffles Difference between Sr.1N HCL 30 Enteric coated tablet 0. Parts: . These standards include ASTM . Glass Standards USP Types Various standards govern the classification of glass into types suitable for specific uses.no Tablet/Capsule 1 2 3 4 5 6 Time (min) Uncoated tablet Water 15 Coated tablet Water 60 0. COATING MACHINE Types of coating Machine (Macleods Pharma) 1) Conventional 2) Auto Coater.8 Hard capsule Water 30 Soft capsule Water 60 Soluble & Water 3 Dispersible tablet Medium 31.No Conventional Coater Auto Coater (Gansons) 1 Open System Closed System 2 Capacity-1.8mm 4 Exhaust on the Upper side Exhaust on the Down side 5 Temperature can not be Temperature can be controlled controlled 6 Coating Pan-12 inch 7 Four pipes – 1) For Atomizing pressure 2) For Needle 3) For Fan Air 4) For Coating solution 32.2 Spray gun nozzle – Diameter mm 0.5 Kg` Capacity-850 gm 3 Spray gun nozzle – Diameter 1.Sr.1N HCL 120 Mixed phosphate 60 buffer pH6.

and USP (United States Pharmacopoeia). Examples of Type I borosilicate glass include Corning® Pyrex® 7740 and Wheaton 180. chemicals.(American Society for Testing and Materials). it does meet or exceed USP Type I requirements. and samples requiring sterilization. USP Type I borosilicate glass is the least reactive glass available for containers. Examples of Type NP glass include Wheaton 810 and 910. USP Type II de-alkalized soda-lime glass has higher levels of sodium hydroxide and calcium oxide. It is also suitable for packaging liquid formulations that prove to be insensitive to alkali. Although Type I borosilicate has the least pH shift of any glass. . Though Corning® Vycor® 7913 is not classified as a Type I glass. The applicability of a particular container to an end use cannot be determined by this criteria alone. All lab glass apparatus is generally Type I borosilicate glass. as even Type I glass can be subject to attack under certain conditions. however it will further enhance the desirable characteristics of an already superior container. sensitive lab samples. USP Type NP soda-lime glass is a general-purpose glass and is used for non-parenteral applications where chemical durability and heat shock are not factors. and 400. UN-buffered products. Other general criteria has been developed to assist with the use of the USP classifications in selecting containers. In most cases Type I glass is used to package products which are alkaline or will become alkaline prior to their expiration date. It can be used for products that remain below pH 7 for their shelf life. These containers are frequently used for capsules. This surface enhancement may become especially important for small containers because of the high ratio of container surface area to the volume of the container contents. Type III glass should not be used for products that are to be autoclaved. but can be used in dry heat sterilization. It can be used for all applications and is most commonly used to package water for injection. USP Type III soda-lime glass is acceptable in packaging some dry powders which are subsequently dissolved to make solutions or buffers. Surface treatment is not usually required. tablets and topical products. It is less resistant to leaching than Type I but more resistant than Type III. there still may be some sensitivity with certain packaged products. Care must be taken in selecting containers for applications where the pH is very low or very high. Examples of Type III soda lime glass include Wheaton 800 and 900. 200. The following classifications were determined by USP criteria. EP (European Pharmacopoeia).

In User mode the number of drops can be programmed from 1 to 9999. The on-line menus and status indicators make the operation of the . Each station is directly driven by independent motors to ensure a maintenance. The test can be performed in two different modes USP mode and USER mode in both test methods. results like Tapped Density. To ensure a free drop of the cylinder from the required height. the two stations are provided with virtually friction-free bearings. test will run in selected method with set number of taps.Tap Density apparatus (USP) Two station tap density tester supporting both USP I and USP II Methods of testing. During the test the user is guided through a series of prompts on the LCD display. At the end of the test. A simultaneous rotating and tapping motion minimizes any possible separation of the mass during tapping down. In USP mode.free drive. USP I or USP II.33. The test can be performed in either of the methods i. Compressibility Index and Hausner Ratio are calculated and displayed.e. The test can also be performed as per ASTM standards using the optional adapter for cylinder holders. Two different cylinder holders with snap-lock mechanism are designed to hold the 100 ml and 250 ml cylinders. The unit allows any one test to be performed at a time.

Relative humidity is normally expressed as a percentage and is defined in the following manner RH = p(H2O)/p*(H2O) Multyply by100 where: RH is the relative humidity of the mixture being considered. At this point the moisture level of a material can be expressed in terms of equilibrium relative humidity (ERH). Water activity (aw). 55 VA. 55 VA (on request) 360 L x 320 W x 200 H (Approx. ASTM (optional) 2 300 (USP I ). 250 (USP II) 14 ± 2 (USP I) & 3 ± 0. 100/110 V AC. and p*(H2O) is the saturated vapor pressure of water at the temperature of the mixture. or equilibrium relative humidity (ERH) is a measure of the free water in a pharmaceutical dosage form. Equilibrium Relative Humidity or the ERH :The relative humidity of an air-water mixture is defined as the ratio of the partial pressure of water vapor in the mixture to the saturated vapor pressure of water at a prescribed temperature.instrument user friendly. This Equilibrium Relative Humidity or ERH balance is achieved when vapour pressures (within the material and the environment) have equalized. Drop Height (mm) Tap Count Range Cylinders Cylinder Holders Type of Drive Display Power Supply Dimensions (mm) Weight USP I and USP II. of Stations Drops / Min. It is defined as the ratio of the water .9999 100 & 250 ml (1 each) For 100 & 250 ml 1 each Direct drive with Stepper motor 24 x 2 Alphanumeric Dot Matrix backlit LCD 220/230 V AC.3 (USP II/ASTM) 1 .) without the cylinders 34. 50/60 Hz. Equilibrium Relative Humidity or the ERH of a material is the relative humidity when the movement of moisture from a material to the environment (and vice versa) have equalized. Specifications Test Methods No. The drops / minute is validated on-line and displayed by the instrument. p(H2O) is the partial pressure of water vapor in the mixture. 50/60 Hz.

crystallinity resulting in polymorphism. The water molecules are located at various sites within the mixture of ingredients. The excipients may preferentially bind moisture and make the dosage form less susceptible to changes in relative humidity during manufacture. nutraceuticals and photochemicals. Great care must be taken to prevent aggregation under pharmaceutically relevant conditions. thus extending shelf life. Hygroscopic excipients (starch. storage or patient use. and dissolution rate of dosage forms of pharmaceuticals. These processes involving water are driven by relative humidity and may be dependant on the ERH of the materials. Knowledge of the behavior of microorganisms in pharmaceutical products at different aw levels is important in meet Federal Food. aggregation and conformational changes from occurring is important to deliver the correct dosage . Chemically the active ingredient can degrade resulting in undesired impurities. Stability Protein. Water associated with a substance is classified as either free or bound. Microorganisms have a limiting aw below which they cannot grow. microbial stability. Less understood is the movement of water molecules between ingredients. Sophisticated techniques are being developed to understand the role played by water molecules in pharmaceutical products. Equilibrium relative humidity is water activity expressed as a percentage.vapor pressure of the substance (p) to the vapor pressure of pure water (po) at the same temperature. aw = p/po . flow properties. It is known that these products lose and gain water from the atmosphere. Most proteins. keratin) and various synthetic hydrogels. enzymes and biopharmaceuticals also must maintain integrity to remain active. Microbial Growth Water activity is a better index for microbial growth than water content. ERH = aw x 100. hardness. Drug and Cosmetic Laws. cellulose and magaldrate) have successfully been formulated for use with moisture sensitive drugs. Component Compatibility The importance of water activity as opposed to total water is used in preformulation compatibility studies involving moisture-sensitive drugs. shipment. proteins. The water activity concept has served the microbiologist and food technologist for decades and is the most commonly used criterion for safety and quality. biopharmaceuticals.g. enzyme and biopharmaceutical stability is influenced significantly by water activity due to their relatively fragile nature. Pharmaceutical Importance of ERH Water activity (aw) influences the chemical stability. This is also applicable to other polymer systems of Pharmaceutical interest. the extent of which depends on the ingredients themselves. compaction. such as proteins (gelatin. Maintaining critical water activity levels to prevent dissolution. Physical changes can occur e. Water activity over water content provides useful information for formulation design. manufacturing conditions and packaging requirements. .

When tablets are in the process of equilibrating to a higher or lower value.Additional Applications Water activity of powders effects the flow. or the tablets have a coating. Water activity also has uses in design and development of coating technology. Water Activity Values of Typical Pharmaceutical and OTC Drug Products . aw is used in the study of shelf-life. Understanding the response of solid dosage forms to changing environments aids in determination of formulation and packaging requirements. compaction and strength properties of solid dosage forms. the tablets should be crushed in order to obtain an accurate free moisture level for the entire tablet. aging and packaging requirements of pharmaceuticals. Additionally. caking.

.

the consistency of which may be adjusted by the addition of substances such as glycerol or sorbitol. —cachets. antimicrobial preservatives. —modified-release capsules. The capsules may bear surface markings. coloring matter authorised by the competent authority and flavoring substances may be added.35. They are intended for oral administration. The capsule shells are made of gelatin or other substances. usually containing a single dose of active substance(s). Capsule Capsules are solid preparations with hard or soft shells of various shapes and capacities. Several categories of capsules may be distinguished: —hard capsules. —soft capsules. sweeteners. —gastro-resistant capsules. . Excipients such as surface-active agents. opaque fillers.

TABLE 1 Weight of active Subtract from the Add to the upper ingredients in each lower limit for limit for samples capsule samples of of 15 10 5 15 10 5 0. For limits other than 90 to 110%. Weigh the shell.2 0. Open the capsule without losing any part of the shell and remove the contents as completely as possible.5 0. may be used.6 1. a smaller number.TESTS Content of active ingredients: Determine the amount of active ingredient(s) by the method described in the Assay and calculate the amount of active ingredient(s) in each capsule. which must not be less than 5. The requirements of Table 1 apply when the stated limits are between 90 and 110%. Not more than two of the individual weights deviate from the average weight by more than the percentage deviation shown in Table 2 and none deviates by more than twice that percentage. Determine the average weight.2 0. or such other number as may be indicated in the monograph. are used in the Assay. The result lies within the range for the content of active ingredient(s) stated in the monograph.8 1.3 0.2 0.5 1.3g 0.0 Uniformity of weight: This test is not applicable to capsules that are required to comply with the test for Uniformity of content for all active ingredients.8 More than 0. TABLE 2 Average weight of Percentage deviation capsule contain Less than 300 mg 300mg or more 10 7.5 And less than 0. proportionately smaller or larger allowances should be made.2 0. Repeat the procedure with a further 19 capsules.2 0.12 g or less 0.4 1.12g 0. Weigh an intact capsule.3g or more 0. This range is based on the requirement that 20 capsules.8 0. but to allow for sampling errors the tolerances are widened in accordance with Table 1.3 0. Where 20 capsules cannot be obtained. The weight of the contents is the difference between the weighings.7 1.1 0.5 . To remove the contents of a soft capsule the shell may be washed with ether or other suitable solvent and the shell allowed to stand until the odour of the solvent is no longer detectable.

Uniformity of content: This test is applicable to capsules that contain less than 10 mg or less than 10% w/w of active ingredient. a buffer solution of pH 6. unless otherwise justified and authorised. without the discs. For capsules containing more than one active ingredient carry out the test for each active ingredient that corresponds to the afore-mentioned conditions.8 R. the results are invalid.35 g of pancreas powder R per 100 ml of buffer solution) may be used. The test should be carried out only after the content of active ingredient(s) in a pooled sample of the capsules has been shown to be within accepted limits of the stated content. GASTRO-RESISTANT CAPSULES For capsules with a gastro-resistant shell carry out the test for disintegration with the following modifications. Use water R as the liquid medium. Repeat the test on a further 6 capsules omitting the discs. Disintegration (Hard capsules) Hard capsules comply with the test for disintegration of tablets and capsules (2. Repeat the test on a further 6 capsules omitting the discs. 36.1). Powder flow Angle of Repose (Φ) is the maximum angle between the surface of a pile of powder and horizontal plane. Liquid active substances dispensed in soft capsules may attack the disc. 0.1 M hydrochloric acid or artificial gastric juice R may be used as the liquid medium. 0. Add a disc to each tube.8 with added pancreas powder (for example. When justified and authorised. Soft capsules Soft capsules comply with the test for disintegration of tablets and capsules (2. If the capsules fail to comply because of adherence to the discs. unless otherwise justified and authorized. No capsule shows signs of disintegration or rupture permitting the escape of the contents. When justified and authorized. or other such time as may be authorised. The time of resistance to the acid medium varies according to the formulation of the capsules to be examined. It is usually determined by Fixed Funnel Method and is the measure of the flowability of powder/granules. a disc may be added. It is typically 2 h to 3 h but even with authorised deviations it must not be less than 1 h. Add a disc to each tube. When justified and authorised. Operate the apparatus for 60 min. Operate the apparatus for 30 min. the disc may be omitted. Use 0. Examine the state of the capsules.9. .1 M hydrochloric acid or artificial gastric juice R may be used as the liquid medium. Use water R as the liquid medium. If the capsules fail to comply because of adherence to the discs. Operate the apparatus for 30 min.1). If the capsules float on the surface of the water. in such circumstances and where authorized. Replace the acid by phosphate buffer solution pH 6.9. 0.1 M hydrochloric acid as the liquid medium and operate the apparatus for 2 h. the results are invalid.

18 1.26-1. It is usually predicted from Hausner Ratio and Angle Of Repose Measurement.00-1.46-1.11 1.59 >1.34 1.45 1. Hausner Ratio Flow property is very important parameter to be measured since it affects the mass of uniformity of the dose. Compressibility is a measure that is obtained from density determinations.Φ = tan-1 (h / r) where.35-1.19-1. h = height of heap of pile r = radius of base of pile Flow property Excellent Good Fair Passable Poor Very poor Very very poor Compressibility index Compressibility is the ability of powder to decrease in volume under pressure. Hausner Ratio = Tapped Density / Bulk Density Scale for CI & HR CI < 10 11-15 16-20 21-25 26-31 32-37 >38 Flow property Excellent Good Fair Passable Poor Very poor Very very poor HR 1. % Compressibility = (Tapped density – Bulk density/Tapped density)*100 Compressibility measures gives idea about flow property of the granules as per CARR’S Index which is givan in table.12-1.60 Angle of repose(degree) 25-30 31-35 36-40 41-45 46-55 56-65 >66 .25 1.

10 ml 0.15 ml 0.70 ml 0.265 1/4 No.06 1 7/8 3/4 5/8 0.0 ml 2.5 mm 11.9 0.15 ml 0.63 0.5 mm 25 mm 22.224 0.90 ml 1.12 1 0.10 ml 0.15 2.6 5 5 4.75 mm 4 mm 3.3 mm 5. 70 4 5 6 7 8 10 12 14 16 18 22 25 30 36 44 52 60 72 8 6.12 2 1 3/4 1 1/2 1 1/4 1. 14 No.8 1.25 1.24 2 1.3 6. 18 No.18 mm 1 mm 850 µ 710 µ 600 µ 500 µ 425 µ 355 µ 300 µ 250 µ 212 µ 5 4.0 ml 10 ml 20 ml 30 ml 50 ml or more For mobile liquids 0.4 mm 19 mm 16 mm 13.24 4 3 1/2 3 2 1/2 2.8 0.0 ml 5.5 No.7 mm 1.5 mm 8 mm 6. 25 No.5 2.3 6. 30 No.4 mm 1.15 3. 20 No.50 ml 0.6 1.5 2.4 0.5 0. 40 No. 10 No.6 mm 4.5 mm 26.36 mm 2 mm 1.3 6.5 ml 1.3 5. Injection Recomended excess volume to be added (USP): Label size 0.30 ml 0.37.55 3.60 ml 0.8 1.25 ml 0.50 ml 0.4 1.80 ml 2% For viscous liquids 0. 60 No.28 0.5 4.55 3.16 0.2 mm 12. 4 No.2 0.12 ml 0. 5 No. 7 No.56 0.6 1.53 1/2 7/16 3/8 5/16 0. 12 No. 50 No. 3.7 mm 6.14 . 45 No.5 mm 31. 16 No.8 2.5 4 3.55 3. 8 No.2 mm 9.20 ml 3% 38.315 0. 6 No. STANDARD MESH SIEVE SIZES Sieve Designation Standard Sieve Designation Alternate "Mesh" ASTM Sieve Designation Alternate "Mesh" BSS Nominal Wire Diameter (mm) 125 mm 106 mm 100 mm 90 mm 75 mm 63 mm 53 mm 50 mm 45 mm 37.45 0.35 mm 2.71 0.8 mm 2. 35 No.

ic a g N e Z a m b ia . N e w a cAi v e s a lia n / t u str P rO d u a n ic o n t a i n i n g e sZa b lla n d d a n d o ce c t s c t ea is h e s t a b le s u b s ta n c e s 1 s m a lle r P ilo t o f u ll s c a le – rN d wc t i o n p o eu D iff e r e n t p r o d u c t io n b a tc h e s •O •O •O •O U S F D A n n n n g e e e o in g b a tc b a tc b a tc s ta b ility N o . n o . 325 No.1 0.032 0. 80 No.063 0.02 39. 450 No. A p p lic a b ility T u rk e y Awfrd r u n s u b s t a n c e s S o u th A fric a . C a n a d a . Stability Testing (Climatic Zone. 635 85 100 120 150 170 200 240 300 350 400 - 0. P a p u a G 2 in ea u 3 G u id e lin e IC H W H O C h ile .045 0.028 0. 500 No. G hla n a . o f b a tc h B o tsw a n a . 400 No. F iji.025 0. V en e zu e la In d ia .09 0. 1 s m a lle r C P M P B u lk d r u g s u b s t a n c e s S im p le d o s a g e fo r m s O th e r s . in c lu d in g c o m p le x d o s a g e f o r m s a n d d r u g p r o d u c t s w it h o u t s ig n ific a n t b o d y o f in f o r m a t io n E x is t in g a c tiv e s u b s ta n c e s C o n v e n tio n a l d o s a g e fo r m s c o n ta in in g s t a b le a c tiv e s C r it ic a l d o s a g e fo r m s ( p r o lo n g e d r e le a s e fo r m s ) o r w h e n a c t iv e s u b s t a n c e s a r e k n o w n to b e u n s t a b le Batches to be tested: . U n ite d S ta te s A sia n C h in a . J a m a ic a . N e w d ru g p ro d u c ts Z im b a b w e P r o d u c t s c o n ta in in g e a s ily d e g r a d a b le A u stra lia .03 0. Evaluation) Distribution of nations into different climatic zones: R e g io n E uropean A m e r ica n Z o n e s I & II A ll co u n tr ie s Z o n es III & IV B r a zil.05 0.071 0. 200 No. J a p a n . 230 No. S rM L a n k a S i z e & t y p e i in . 100 No. 140 No. 120 No.c a l e 3 P i ot s U ganda 3 2 p ilo t s c a le . P h ilip p in e s.180 µ 150 µ 125 µ 106 µ 90 µ 75 µ 63 µ 53 µ 45 µ 38 µ 32 µ 25 µ 20 µ No.o f b a tc h e s W H O r e q u ir e m e n t h per year h a lte rn a te y e a r (fo r s ta b le p ro d u c ts ) h e v e ry 3 – 5 y e a rs (if s ta b ility p ro file is a v a ila b le ) 1 1 3 2 or 3 2 3 P ilo t s c a le P ilo t s c a le 2 p ilo t s c a le .125 0. 170 No. 1 s m a lle r P r o d u c t io n s c a le P ilo t s c a le 2 p ilo t s c a le .036 0. 270 No.

SIGNIFICANT CHANGE What does significant change means.EVALUATION OF STABILITY DATA TO ESTABLISH SHELF LIFE . For Drug Substance: Failing to meet its specification..For Drug Substances X Long Term (9 months OK) Long Term (12 months OK) Long Term (18 months OK) Long Term (24 months OK) Long Term (36 months OK) Y y = 2x Shelf life / re-test date is 18 months y = 2x Shelf life / re-test date is 24 months y = x + 12 Shelf life / re-test date is 30 months y = x + 12 Shelf life / re-test date is 36 months y=x No extrapolation beyond 36 months Accelerated (6months) Accelerated (6months) Accelerated (6months) Accelerated (6months) Accelerated (6months) EVALUATION OF STABILITY DATA TO ESTABLISH SHELF LIFE For Drug Products RE-TEST DATE For Drug Substances If accelerated stability data for 6 months is NOT OK.For Drug Products RE-TEST DATE .5 months y=x+3 Shelf life / re-test date is 12 months Accelerated (6months) Accelerated (6months) Accelerated (6months) 40.5x Shelf life / re-test date is 13. X Intermediate 12 months OK Intermediate 9 months OK Intermediate 9 months NOT OK & if long term 9 months OK Y y = 1.5x Shelf life / re-test date is 18 months y = 1. . For Drug Products: 5% assay variation from its initial value..

a protected control sample (wrapped in aluminum foil) may be exposed side by side. This can be monitored by either Quinine actinometry.Components and Composition 2. Batch Size (Scale-Up/Scale-Down) 4. Any degradation products exceeding acceptance criteria. xenon or metal halide lamp. calibrated radiometers or lux meters 2. 42. Types of tablets 1:-ORAL TABLETS FOR INGESTION: Standard compressed tablets B) Multiple compressed tablets A) Layered tablets – two to three component system. Manufacturing (Equipment/Process) Level I changes: Which are unlikely to have any detectable impact on formulation quality and performance Level II changes: Which may have significant impact on formulation quality and performance Level III changes: Which have a significant impact on formulation quality and performance.Failure to meet the acceptance criteria for potency when using biological / immunological procedures. B) Compression coated tablets – tablet within a tablet.WHAT IS SUPAC GUIDANCE? •A communication that represents the best scientific judgement of the Agency at this time regarding certain scale-up and post-approval issues: •TYPES OF SUPAC CHANGES 1.Light source: Option 1: Artificial daylight fluorescent lamp combining visible and UV outputs. Photo stability . C) Inlay tablet – coat partially surrounding the core.To exclude the thermal effect.Overall illumination of not less than 1. . Failure to meet acceptance criteria with respect to: 1 Appearance 2 Color 3 Phase separation 4 Re-suspendibility 5 Caking 6 Hardness 7 pH 8 Dissolution on 12 units Some acceptable factors such as softening of suppositories & melting of creams may be accepted at accelerated conditions. Site Changes 3. 41. 43. or Option 2: A cool white fluorescent lamp & a near UV fluorescent lamp having a spectral emission range from 320 nm to 400 nm Level of exposure for stability study: 1.2 million lux hours and an integrated near UV energy of not less than 200 watt hours/m2.

sucrose. which under compaction form a cohesive mass or a compact. Liquid glucose. HPMC. Pregelatinised starch. Alginic acid. Colonic tablets F) Chewable tablet G) Dispersible tablet 2: -TABLETS USED IN THE ORAL CAVITY A) Lozenges and troches B) Sublingual tablet C) Buccal tablet D) Dental cones E) Mouth dissolved tablet 3: .TABLETS ADMINISTERED BY OTHER ROUTES: A) Vaginal tablet B) Implants 4: -TABLETS USED TO PREPARE SOLUTION Effervescent tablet Hypodermic tablet Soluble tablet 44. PH 102) (10-20). Starch 1500(5-15). which is referred to as a tablet. Cellulose. Polyvinyl alcohol. PVP. A disintegrant is added to most tablet formulations to facilitate a breakup or EXCIPIENT Starch. Microcrystalline cellulose. Tablet excipient: TYPE EXCIPIENT Diluents or Fillers FUNCTION Diluents make the required bulk of the tablet when the drug dosage itself is inadequate to produce tablets of adequate weight and size. mannitol. HPC. Powdered cellulose. Binders are added to tablet formulations to add cohesiveness to powders. Calcium phosphates Lactose. sorbitol etc. Avicel®(PH 101. Tragacanth. Binders or Granulating agents or Adhesives Disintegrants . Starch paste. PEG. Sucrose. Sodium carboxy methyl cellulose. Acacia. thus providing the necessary bonding to form granules. Polymethacrylate Starch USP(5-20).Gastro retentive Tablet II.Modified release tablet Delayed action tablet Targeted tablet I. Gelatin.

SLS. Na CMC.25%).Emcosoy®. Waxes.75%) are also successfully used to induce flow. Polyplasdone®XL . syloid. Na Streate) Talc. Sterates. hydrated sodium silioaluminate (0. Ca. Corn starch.5-5). Polyplasdone®(XL)(0. Wetting agents are added to tablet formulation to aid water uptake during disintegration and assist drug dissolution. Streates(Mg.Sodium starch glycolate Explotab®. Explotab®(2-8). Crosspovidone. Calcium silicate Antifrictional Agents Lubricants Antiadherents Glidants Lubricants are intended to reduce the friction during tablet formation in a die and also during ejection from die cavity. Ac-DiSol® . Soy polysaccharides. HPMC (5-10).5-5). Polyplasdone® . Cellulose and its derivatives. Alginates. Glyceryl Behapate. Sodium diisobutyl sulfosuccinate (used for hydrophobic drugs) MISCELLANEOUS Wetting agents Dissolution Dissolution retardants as the Waxy material like . Amberlite® (IPR 88) (0.Primellose® . Solutab® . colloidal silica i.Polyplasdone®XL10. Colloidal silica.NF Satialgine®. Microcrystalline cellulose (MCC). pyrogenic silica (0. Alginic acid (1-5). Streate. Crosspovidon M® . Kollidon® . Streate. Liquid paraffin Talk.510). Solka floc® (5-15). Superdisintegrants Crosscarmellose®. DL-leucine Starch (10%) . Methyl cellulose. Antiadherents are added to reduce sticking or adhesion of any of the tablet granulation or powder to the faces of the punches or to the die wall.e. Primogel® Alginic acid.disintegration of the tablet when placed in an aqueous environment.Vivasol®. Glidants are intended to promote the flow of tablet granulation or powder mixture from hopper to the die cavity by reducing friction between the particles.Nymce ZSX® . Na alginate (2. SLS.

Butylated Hydroxy Anisole (BHA) . sodium bicarbonate. Adsorbents are capable of retaining large quantities of liquids without becoming wet. Dihydroxy Ethyl Glycine. sodium metabisulfite . Dissolution enhancers as the name suggest. Antioxidants are added to maintain product stability. fluid extracts and eutectic melts to be incorporated into tablets. Indigotine. retards the dissolution of active pharmaceutical ingredient(s). Tartrazine. butyl phydroxy benzoate are used as preservatives. Erythrosine. enhance the dissolution rate of active pharmaceutical ingredient(s). citric acid . and tartaric acid . which are often required to initiate oxidative reactions. Preservatives are added to tablet formulation in order to prevent the growth of microorganisms. Flavours are added to tablet formulation in order to make them palatable enough in Oil or aqueous Flavours are added. propyl. Buffers are added to provide suitable micro environmental pH to get improved stability and / or bioavailability. Sunset yellow. . alpha-tocopherol . they act by being preferentially oxidized and gradually consumed over shelf life of the product. and sodium citrate. product identification and for production of more elegant product. they act by forming complexes with the heavy metal ions. Allura red AC. Brilliant blue. Surfactants anhydrous calcium phosphate. ethylene diamine tetra acetic acid .retardants Dissolution enhancers Adsorbents Buffers Antioxidants name suggest. calcium carbonate. Chelating agents Preservatives Colours Flavours Chelating agents are added to protect against autoxidation. Colours are added to tablet formulation for following purposes: to disguise off colour drugs. Povidone. sodium bisulfite . kaolin. magnesium silicate. bentonite. Ethylenediamine tetracetic acid and its salts. starch. Butylated Hydroxy Toluene (BHT) . ascorbic acid and their esters . this property of absorbent allows many oils. stearic acid and their esters (for controlled release of drug) Fructose. magnesium oxide and silicon dioxide. Fast Green. magnesium carbonate. Citric Acid and Tartaric Acid Parabens like methyl. benzyl.

Saccharine. Sweeteners are added to tablet formulation to improve the taste of chewable tablets. Cyclamate. Aspartame etc. Povidone (N 5-10). Mannitol.3-2%).4). Carbomer (A 0. and thereby Facilitate the wetting of each particle. suspensions to Sodium increase viscosity and retard carboxymethylcellulose sedimentation. carrageenam (A 1-2) A protective colloid is a polymeric suspending agent absorbed on the surface of a hydrophobic suspension particle giving the particle a hydrophilic surface. Surface tension of an Polysorbate 80 aqueous medium. Docisate surfactants that reduce the sodium (Anionic). 5%. one would prefer a uniform Size.1concentration range of 1 to 0.5-5). surfactants. Lactose. Sucrose. The goal is to displace air from the particle surface and to separate each particle from adjacent particles Using the minimum concentration necessary Suspending agents are Methylcellulose (N1-5%). Protective Colloid Flocculating Agent . 45. Flocculating agents enable suspension particles to link together in loose aggregates or flocs. and polymers. however size reduction is carried out for uniform size distribution. Dextrose.5-2). Wetting agents are SLS (Anionic). SUSPENSION INGRIDIENTS TYPE OF INGREDIENT Drug Wetting Agent FUNCTION EXAMPLE Suspending Agent Ideally. Mg Allu.Bentonite (A 1negatively charged and 6). coat (Nonionic) the surface of suspension particles. Xanthan gum (A 0.Sweeteners case of chewable tablet by improving the taste. Most (A 1-2). These flocs settle Electrolytes. Silicate (A generally effective in a 0. materials added to HPMC (N 0.3-3). MCC with Na suspending agents are either carboxymethylcellulose neutral or (A 0.

Sucrose.004-0. Methylparaben (0. Benzalkonium Chloride (0.02). Sorbic Acid (0. Preservative Ethanol (>20).1-0. Sodium Saccharine.05) Buffer Flavor Colour The optimal pH is chosen to minimize solubility of the drug.2). Quaternary Amines. Sweetener Sweeteners are added to suspensions to produce a more palatable preparation. Benzoic Acid (0. Parameters used in IVIVC . Propylene Glycol (15-30). Sequestering agents may be necessary to bind metal ions to control oxidative degradation of Either the drug or other ingredients.5). Mannitol. control stability of the drug. Sequestering Agent 46. Preservatives are required in most suspensions because suspending agents and sweeteners are good growth media for microorganisms. Aspartame etc.05-0. to cover the taste of the drug and other ingredients.5-3).rapidly but form a large fluffy sediment which is easily redispersed. and to ensure compatibility and stability of other ingredients Flavoring agents enhance patient acceptance of the product.2). which is particularly important in pediatric patients Colorants are intended to provide a more aesthetic appearance to the final product. Propylparaben (0. Benzyl Alcohol (0.

When a voltage is applied to the solution in which particles are dispersed. particles are attracted to the electrode of the opposite polarity. forming a cloud-like area. Outside the fixed layer. . or internal side of the "sliding surface". there are varying compositions of ions of opposite polarities. accompanied by the fixed layer and part of the diffuse double layer. This area is called the diffuse double layer. and the whole area is electrically neutral. Zeta potential Colloidal particles dispersed in a solution are electrically charged due to their ionic characteristics and dipolar attributes.47. Each particle dispersed in a solution is surrounded by oppositely charged ions called the fixed layer.

which serves as the vehicle. or waxy solids. particles tend to aggregate. such as beeswax or paraffin wax. EMULSION INGRIDIENTS TYPE OF INGREDIENT Drug FUNCTION EXAMPLE Oil phase A drug can be dissolved or dispersed in either the oil or aqueous phase of an emulsion.Zeta potential is considered to be the electric potential of this inner area including this conceptual"sliding surface". Zeta Potential (Smoluchowski’s Formula) 48. . As this electric potential approaches zero. The consistency of the oil phase Vegetable or mineral oil can be altered by the addition of waxes. This mode of drug incorporation can be used for oral and/or topical administration.

propylene glycol. Acacia. corn syrup and Sucrose. Preservatives are required in most emulsions because thickening (suspending) agents. Emulsions are generally not colored with the exception of some topical products.g. or esters. Alpha tocopherol O/W Acacia. Pot. Sweeteners are added to emulsions to produce a more palatable preparation. Thickening agents are materials added to an emulsion to increase viscosity and retard sedimentation. Lipid soluble: Butylated hydroxyanisole. which is particularly important for pediatric patients. Butylated hydroxytoluene. . Humectants are water soluble polyols that prevent or hinder the loss of water from semisolid emulsions. Metabisulfite. acids. sorbitol Emulsifiers Emulsifiers are substances that Water soluble: Na. sodium saccharin and aspartame. The optimal pH is chosen to ensure activity of the emulsifier. emulsifiers and sweeteners are good growth Media for microorganisms. Tragacanth Sorbitol. or glycerol monostearate.Aqueous phase Thickening agents Sweeteners Preservative Buffer Flavour Colour Sequestering agents Humectants Antioxidants such as fatty alcohols. The aqueous phase is composed of the water soluble components in a formulation. cetyl alcohol. Antioxidants are often added to prevent oxidation of vegetable oils and/or the active drug. Flavoring agents enhance patient acceptance of the product. Lacithin. e.. Glycerin. control stability of the drug and to ensure compatibility and stability of other ingredients. Bisulfite. stearic acid. Colorants are intended to provide a more aesthetic appearance to the final product. Sequestering agents may be necessary to bind metal ions in order to control oxidative degradation of either the drug or other ingredients.

SLS.have the ability to concentrate at the surface of a liquid or interface of two liquids. Depends on phase vol. Ratio. Polysorbate 80. Literature Search Pharmacology 1) Physician desk reference 2) Martindale Extra Pharmacopoeia 3) Therapeutic Drug 4) British National Formulary 5) ABPI compendium of data sheet and summaries of product characteristic 6) Anatomic Therapeutics Chemicals (ATC) and Defined daily dose (DDD) classification Reference: http://www. Triethanolamide stearate.Bentonite.no/atcddd a) Anatomical group b) Pharmacological or Therapeutic subgroup c) Chemical subgroup d) Therapeutic indication: . Potassium laurate. Magnesium hydroxide. Surfactants are added like Sorbitan monoleate. Polyoxyl 40 stearate. Sorbitan fatty acid esters.W/O Cholestrol. many of them reducing the surface or interfacial tension.whoccc.

htm http://www. Eur.fda. and Clearance Renal.htm http://acronyms.com/search3.thefreedictionary.gov/cder/OPS/BCS_guidance.dissolutiontech. Salivary and Other form of excretion Metabolism Bioavailability Effect of Physiological changes with age sex and disease on the ADME Reported pharmacokinetics parameter: a) Vd b) Kel c) AUC d) Clearance e) Tmax f) Cmax g) T1/2 h) Linear or Non linear Kinetics 9) Minimum Effective concentration /Therapeutic range 10) Reported BCS Class Reference: http://www.htm http://www. Bilayer.gov/cder/guidance/3618fnl.Biopharmaceutical Factors 1) 2) 3) 4) 5) 6) 7) 8) Mechanism of action Effect of diffusion.tsrlinc.) f) Japanese pharmacopoeia (JP) Other Literature a) Merck index b) Florey analytical profile c) US patent d) EU patent e) WO patent f) Journal / conference .com/Biopharmaceutics+Classification http://www.com/assets/adeptiv/upload/attach/Copy%203%20of% 11) Reported pka values 12) Effect of Food Active ingredient Pharmacopoeial status a) Indian pharmacopoeia (IP) and Addendum to Indian pharmacopoeia b) USP and supplement of US pharmacopoeia and USP forum and USP/NF c) British pharmacopoeia (BP) and Addendum to British pharmacopoeia d) International pharmacopoeia e) European pharmacopoeia (Ph. physical properties of drug and body on Distribution Biotransformation.cfm http://www.com/DTresour/0502art/DTMay02_art1. First pass effect. Mammary.absorption.fda.

If yes record the desired method on control the particle size distribution Whether API has tendency of degradation via hydrolysis.1) Active ingredient INN Name 2) Chemical name 3) IUPAC name 4) Molecular structure 5) Molecular formula 6) Molecular weight 7) CAS registry No. 8) Toxicity and Hazard class 9) Storage condition 10) Handling precaution 11) Appearance 12) Solubility in organic solvent (Having Carbon) 13) Solubility in inorganic solvent (HCl. Report the extent of degradation. isomerisation. photolysis and polymerization. IF yes. does it required controlling isomeric purity with reference to therapeutic values Whether API has reported to have incompatibility with known excipients . probable degradation and impurities Whether API exhibits isomerisation. oxidation. Record the characteristic 2Ө value and d spacing and melting point for various polymorphs/solvates/hydrate/pseudopolymorph Whether API required control on particle size distribution. H2SO4) 14) Solubility in water 15) Identification 16) PH of 1%w/v solution or suspension at 250C 17) Moisture 18) LOD 19) Crystallinity 20) Melting point 21) Polymorphism 22) Solvate/Hydrate 23) Specific optical rotation 24) Sulphated ash 25) Residue on ignition 26) Heavy metal 27) Related substance (RS) 28) Assay 29) Particle size distribution (Sieve analysis plot frequency distribution curve) 30) Sieve analysis 31) Bulk density 32) Tapped density 33) Intrinsic dissolution 34) Particulate dissolution 35) Bacterial Endotoxine 36) Hygroscopicity Note: If polymorphism reported. heating. which form is included in product specification EU or US patent If there any advantage of specific polymorph over other with respect to stability and bioavaila.

Use the highest dose streanght in 10 ml of following. D50. It is done at least at: pH = pKa pH = pKa +1 pH = pKa –1 pH=1 pH=7 To be performed if sufficient data not available in literature.Aqueous solubility to be checked at various pH levels ranging from 1 to 8 at 37±10C. Check the solubility using USP criteria of solubility determination in various solvents at 250C±10C Water Methanol Ethanol Propranol Dimethyl sulphoxide (DMSO) Dimethyl formamide (DMF) Acetone Tetrahydrofurane(THF) Methylene chloride (MDC) 2. the maximum volume can be 250 ml .pH solubility profile pKa value Log P value Evaluation of API from different manufacturer 1) FTIR characterization 2) H-1 and C-13 NMR characterization 3) Mass characterization 4) Elemental analysis report 5) XRPD diffract gram 6) DSC thermogram 7) Solid state discription (colour. D90) 14) LOD at… 15) Moisture content 16) Related substance 17) Assay Solubility study: 1. crystalline/amorphous) 8) Bulk density 9) Tapped density 10) Compressibility index 11) Housnor ratio 12) Particle size (sieve analysis. Add measured volume of respective solvent in increament of 10 ml. plot frequency distribution curve) 13) Particle size (D10.

HCl acid buffer pH 1.0 7. Phosphate buffer pH 7. Purified water + 0. Check the solubility in : *Purified water +0.8 9.4.1% SLS 14. Increase the concentration of tween 80 to upto 2% to get the desired solubility Determine the pH of solution in which drug is soluble to maximum extent Determine the saturation solubility point Solubility study 1. Purified water + 0. Phosphate buffer pH 5. Justification for the selection: Following are the basic guideline for the selection of comparator product . Phosphate buffer pH 8.0 12. Increase the concentration of SLS to upto 2% to get the desired solubility *Purified water +0. Stability study of test sample stored at 370C to be done against freshly prepared solution at predecides interval for 8 hr Report the assay and % degradation.6.In case of aqueous solubility is less than 0.5% SLS 15. 0.8 and 8. Water pH stability profile Determine the stability of 2%w/v solution of suspension at pH 1. and therapeutics equivalence of test product witj that of reference product.1% tween 80.2 5. bioequivalence.5.0 6.2 4.01N HCl 2.1% SLS.8 10. HCl acid buffer pH 2. Stability has to be determined using stability indicating HPLC assay method.2 11.5 13.1N HCl 3. the requirement is to establish the pharmaceutical equivalence. Selection of comparator product and its dissolution criteria and its dissolution criteria and preparation of tentative specification for target product For development of generic version of the reference drug product.3 %. Acetate buffer pH 5. 0.0 8. use the solubility improving techniques for improving the in vitro solubility. Phosphate buffer pH 6. Acid phthalate buffer pH 4. Acid phthalate buffer pH 3. Neutralized phthalate buffer pH 5.2.

Mfg date 10. Pack insert 16.1. Shelf life 12. DT 19. Generic name and strength 3. Special handling requirement 14. Product description 5. Reference listed product 3. Storage condition 13. RS 21. Description of packing 15. Instruction for use 6. Batch no 9. Innovator product 2. Label claim 4. Manufacturer name and address 8. Rout of administration 7. Physical description/Dimension/Marking 17. Pioneer product Procure reference product from 2-3 batches from different markets and if possible in smallest and largest pack size 1. Assay API: Excipients compatibility study and Excipients selection API Forced degradation study: Stress factor Heat Conditions 600C Concentration of API# API only Time 15 Days Evaluation parameter Visual &chemical . Method of analysis (compendial /Non compendial) 18. Dissolution medias (1/2/3/4/5 ) 20. Brand name 2. Exp date 11.

1 N NaOH at 250C 3% H2O2 at 250C Rom temp. Xe. Primary packaging materials: Manufacturer’s Name and Address: Sr.In each case.05 M Fe2+ or Cu2+ 2-80C Solid state API 15 Days Visual &chemical Chemical Chemical Chemical Visual & chemical Visual $ Chemical 2:1 in 0.1 N HCL 1:1 in 3% H2O2 1-10 Days 1-10 Days 1-3 hours 2% 4-24 hour solution/suspension over pH range of 1. Dimentional criteria: Shape Neck Finish Observation . Hg.2 to 8. Observation summary and conclusion: Procurement and evaluation of suitable container-closure system Quality control of packaging components A.1 N HCL 2:1 in 0. Parameter Physical characteristics 1.0 1:1 with diluent 1-10 Days 1:1 with solution of metal ions Solid state API 1-10 days 15 Days Chemical If required # . the diluent is either an excipients or all excipients in the formulation in the same ratios as in the formulation. the APIs should be in same ratio as in the FDC.2 million lux.when testing degradability of APIs in combination.Humidity Acid Base Oxidation Solution stability Photolysis (Optional) Metal ions (Optional) Control sample 400C with 5% moisture in sealed glass vial 0. Description 2.1 N HCL at 250C 0.No. solution stability study at different pH Expose the test compound to 1. .hr florescent light and to near UV energy of not less than 200 watt hours/m2. or UVB fluorescent lamp 0. Metal halide.

Vapour transmission rate 6. Metering valve delivery volume Chemical Composition 1. . Associated components: Associated components are packaging components that are typically intended to deliver the dosage form to the patient but are not stored in contact with the dosage form for its entire self life. Materials of construction 2. Unit weight/grammage 5. Design tolerances 4. Light resistant test Performance characteristics 1.Wall thickness 3. A. B. Primary packaging material: Same table as above. Extraction profile for the polymeric and elastomeric components* • *For inhalation drug products for which batch-to-batch monitoring of this is routine.

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