Aristo Pharmaceuticals

Private Limited.

REGULATORY COMPLIANCE
QUALITY CONTROL
 LIST OF EQUIPMENTS/INSTRUMENTS

 pH Meter  IR
 Conductivity meter  GC
 Karl Fischer Titrator  HPLC
 Friabilator  Dissolution Apparatus
 Potentiometer  UV-VIS.
 Polarimeter Spectrophotometer
 Sieve shaker  Disintegration tester
 Hardness tester  Vernier Caliper
 Moisture balance  Sonicator
 Analytical balance  Water Bath
 TOC  Tap density tester
 WORKED ON INTRUMENTS

 pH meter
 Conductivity meter
 KF Titrator
 Friabilator
 Hardness tester
 Analytical Balance
 Disintegration tester
 Dissolution Apparatus
 UV-VIS. Spectrophotometer
 HPLC
 Vernier Caliper
 pH Meter

pH values represent acidity or alkanity of an aq. solution, where, pH as a

measure of hydrogen ion activity is important from the standpoint of stability
or physiological suitability.
 Temp. = 25 ± 2º C.
 Calibration- daily
Calibration is done using buffer solution D (4.01) as primary standard.
Buffers used for calibration- A (1.68), D (4.01), E (6.87), G (9.18), I
(12.45)
Tolerance - ±0.05
 Validity of buffers-
For prepared buffers- 15 days
For readymade buffers- 2 years
 Conductivity Meter

 Conductivity of solution is reciprocal of resistivity, which is defined as quotient

of electric field and density of current (flowing in conducting solution).
It is used to calculate Total Dissolved Solids in liquid.
 For purity of substance.
 Units- Siemens per meter
S/m (International) or µS/cm (generally used), S/cm
 Temperature = 25°±1º C
 Reference material- KCl
 Cell constant- High cell constant for high conductivity. Commonly used
conductivity cells have cell constant – 0.1 cmˉ¹, 1 cmˉ¹, 10 cmˉ¹.
 Conductivity of water for – Purified Water – NMT 2.1 µcmˉ¹
Water for Injection- NMT 1.3 µcmˉ¹
 Conductivity Meter

 Calibration- (temp. – 25° C ± 1°C)

STANDARD SOLUTION LIMIT

Standard solution 0.01 M 1.397 mS cmˉ¹ - 1.544 mS cmˉ¹

( 1.470 mS cmˉ¹ )
Standard solution 0.001 M 139.7 µS cmˉ¹ - 154.4 µS cmˉ¹
(147.05 µS cmˉ¹)
Standard solution 0.002 M 27.937 µS cmˉ¹ - 30.877 µS cmˉ¹
(29.4 µS cmˉ¹)
 Friabilator

 The percentage weight loss after tumbling is referred to as the friability of the tablets.
 Done to test the ability of tablets to withstand mechanical stresses
determines their resistance to chipping and surface abrasion by tumbling them in a
rotating cylinder.
 Drum – internal diameter- 283-291 mm
- Depth- 36 - 40 mm
- Curved projection Inside radius- 75.5 - 85.5 mm
 The drum is attached to the horizontal axis of a device that rotates at 25 ±1 rpm.
Thus, at each turn the tablets roll or slide and fall onto the drum wall or onto each
other.
 For tablets with a unit weight equal to or less than 650 mg, take a sample of
whole tablets corresponding as near as possible to 6.5 gm. For tablets with a unit
weight of more than 650 mg, take a sample of 10 whole tablets.
 Dedusting prior to testing.
 Rotate 100 times.
 Friabilator

 If the results are difficult to interpret or if the weight loss is greater than the
targeted value, the test should be repeated twice and the mean of the three tests
determined.
 A maximum mean weight loss from the three samples of not more than 1.0%
is considered acceptable for most products.
 Calibration- RPM is noted at 1 minute, 2 minutes, 4 minutes.
Acceptance criteria- RPM= ± 1
 Hardness Tester

 Hardness or breaking force, is the force required to cause them to fail (i.e.,
break) in a specific plane.
 Tablets must be able to withstand the rigors of handling and transportation
experienced in the manufacturing plant, in the drug distribution system, and in
the field at the hands of the end users (patients/consumers). Manufacturing
processes such as coating, packaging, and printing can involve considerable
stresses, which the tablets must be able to withstand.
 Thickness calibration- Reference value- 10mm
- Tolerance value- ±0.20 mm
- mean of 5 readings is calculated.
 Hardness calibration- Reference value- 5.0 kg
- Tolerance value- ± 50 gm.
- mean of 5 readings is calculated.
 Disintegration Test

 This test is done to determine whether tablets or capsules disintegrate within

the prescribed time when placed in a liquid medium at experimental
conditions.
 Complete disintegration is defined as that state in which no residue except
fragments of insoluble coating or capsule shell, remains on the screen of the
test apparatus or adhering to the lower surface of the disk, if used.
 Temperature- 37 ± 2° C.
 Beaker- 1000 ml
Basket frequency- 29- 32 cycles/ min.
Distance travelled by the basket between highest and lowest point of
oscillation- 53-57 mm.
 Disks- cylindrical disk made of suitable transparent plastic material.
- have specific gravity between- 1.18 and 1.20.
- disks are used based on the density and dimensions or as specified.
 Disintegration Test

 For disintegration test, single dosage unit is placed in each of the six tubes of the
basket.
 If 1 or 2 tablets fail to disintegrate completely, repeat the test on 12 additional
tablets. The requirement is met if not fewer than 16 of the total of 18 tablets are
disintegrated.
 Disintegration time for –
Coated Tablets- NMT 30 minutes.
Uncoated Tablets- NMT 15 minutes.
Enteric Coated Tablets- (i) operate the apparatus under simulated gastric fluid
for 1 hour. (if the tablet has soluble sugar coating,
immerse the basket in water for 5minutes at room
temperature.)
(ii) After 1 hour of operation in simulated gastric fluid
TS, lift the basket from the fluid and observe the tablets, the tablets show no
evidence of disintegration, cracking, or softening.
 Disintegration Test

(iii) Operate the apparatus, using simulated intestinal fluid TS maintained at 37 ±

2° as the immersion fluid, for the time specified in the monograph.
 Calibration- (i) Up and down oscillation of mechanical device-
29-32 cycles/min.
(ii) Measurement of temperature- by standardized
thermometer- 37± 2°C.
(iii) Calculation of distance travelled by basket between lowest
and highest point of oscillation – 53-57mm.
 Karl Fischer Titrator

Calculation of factor = wt. of water in mg

Vol.(ml) of reagent used in titration
RSD- NMT 1.0%
Moisture content = water factor* V * 100
Wt. of DST (gm)
% Moist content- 15.50- 15.82 % w/w
 Analytical Balance

WEIGHT VARIATION

IP/BP LIMIT USP

80mg or less ±10% 130mg or less

More than 80mg or less ±7.5% 130mg to 324mg

than 250mg

250mg or more ±5% More than 324mg

 Analytical Balance

Accuracy (diff. b/w actual and observed wt.) ( equal

to or not more than 0.10%)
Eccentricity (deviation of wt. from center of
sample) (NMT 0.05%)
Repeatabilty (magnitude) (equal to or not more
than 0.10%)
 RAW MATERIAL QC

Sampling of Raw Material

MATERIAL RECEIVED

DEDUSTING

QUARANTINE GRN QC

SAMPLING TESTING–
EXCIPIENTS (√n+1),
UNDER TEST API (100% testing of
(YELLOW
LABEL) all containers)
TESTING APPROVED
(GREEN LABEL)
APPROVED
RAW MATERIAL QC

PRODUCTION REQUEST GENERATED

WAREHOUSE

PALLET, RLAF

DISPENSING AREA
EXCIPIENT
API
PRODUCTION COLOUR

PACKING

MARKET
 Good Laboratory Practices

GLP

SOP/ STANDARD MANAGEMENT CHEMICALS INSTRUMENT CALIBRATION

FORMATS/LOG
MAINTAINENCE SOURCE LABELLING SCHEDULE FOR
STORAGE & HANDLING CALIBRATION
LOTS AND EVALUATION
MONTHLY,
STOCK SOLUTIONS,
ANALYSIS AND QUARTERLY, YEARLY
VOLUMETRIC
QUALIFICATION SOLUTIONS MONTHLY- ±1 DAY
QUARTERLY- ±3 DAYS
CODING, LABELLING
& DISTRIBUTION YEARLY- +30 DAYS

HANDLING & STORAGE

VALIDITY, EXPIRY