These tests are typically performed in accordance with the guidelines set forth by the United States Pharmacopeia (USP) or other regulatory agencies. The testing procedure for Olanzapine tablets typically includes the following steps By SOP for Finished Product Analysis of Olanzapine Tablet By UV and HPLC Method:
Identification: The tablets are identified by their physical characteristics, including their size, shape, color, and markings.
Assay: The assay determines the quantity of active ingredient (olanzapine) in the tablet. This is done using a validated analytical method such as high-performance liquid chromatography (HPLC).
Dissolution: The dissolution test determines how quickly the tablet dissolves and releases the active ingredient. This is important because the rate of dissolution can affect the bioavailability of the drug.
Uniformity of dosage: The uniformity of dosage test ensures that each tablet contains the same amount of active ingredient. This is done by testing multiple tablets from different parts of the batch.
Related substances: The related substances test identifies any impurities or degradation products in the tablet. This is important because these impurities can be harmful or affect the efficacy of the drug.
Microbial limits: The microbial limits test ensures that the tablet is free of microbial contamination. This is important because microbial contamination can be harmful to patients, especially those with weakened immune systems.
Stability: The stability test determines how the tablet degrades over time under various conditions such as temperature and humidity. This is important to ensure that the tablet remains effective and safe throughout its shelf life.
PURPOSE:
To describe the procedure for analysis at in-process and finished stage of Olanzapine 10mg Tablet.
SCOPE:
This SAP gives a detailed outline for the finished product analysis of Olanzapine Tablet and will cover In process testing activities on a physical, chemical & instrumental basis.
RESPONSIBILITY:
QC Analyst is responsible for physical / chemical testing and preparing standard analytical procedure.
It is the responsibility of QC Manager to assist and ensure Testing Procedure as per SAP and to make certain that this SAP is followed in its entirety, reviewed regularly and revised as necessary.
REFERENCE:
USP 43 NF 38
MATERIAL AND EQIUPMENT:
- HPLC
- UV spectrophotometer
- Dissolution apparatus
- Friability apparatus
- Hardness apparatus
- Disintegration Tester
- Vernier Caliper
- Analytical Balance
- Moisture analyzer
- Mortar and pestle
- Spatula
- Filter Paper
- Magnetic Stirrer & Hot Plate
- Sonicator
- Vacuum Pump
- Glassware
- Methanol AR Grade
- monobasic sodium phosphate
- phosphoric acid
- sodium dodecyl sulfate
- Acetonitrile
- Distilled water
PROCEDURE:
FINAL MIX
SOP for Finished Product Analysis of Olanzapine Tablet By UV and HPLC Method
Description:
yellow color powder.
Procedure: Take 2.0 g of the test sample in a watch glass and observe visually with black background. Check the appearance of color, nature and any visible foreign particles.
Identification:
A- By Infrared Spectroscopy
B- The retention time of the major peak of the Sample solution corresponds to that of the Standard solution, as obtained in the Assay.
Loss on Drying: (By Moisture Analyzer)
Procedure:
Turn on instrument 20 minute before the test. Take 2 g powder spread uniformly on Moisture Analyzer plate. Close the lid and press start button.
NMT 5.0% when determined by LOD Apparatus, Use 2.0 g of powder.
Assay: (Limit: 90%-110%)Compression Weight of Powder/Tablet: 240 mg /tablet
Procedure:
[Note-A few drops of acetonitrile, not to exceed 5%of the final volume, may be added to the Standard solution and Sample solution before final dilution to reduce foaming.]
Buffer 1: 6.9 g/L of monobasic sodium phosphate. Adjust with phosphoric acid to a pH of 2.5.
Buffer 2: 12 g/L of sodium dodecyl sulfate in Buffer 1
Mobile phase: Acetonitrile and Buffer 2 (1:1)
System suitability solution: 0.1 mg/mL of USP Olanzapine RS and 0.01 mg/mL of USP Olanzapine Related Compound A RS in Mobile phase.
Standard solution: 0.1 mg/mL of USP Olanzapine RS in Mobile phase.
Sample solution: Transfer a known quantity of Tablets (NLT5), equivalent to NLT 25 mg of olanzapine, to a suitable volumetric flask. Dilute with Mobile phase to volume, mix, and sonicate for 10 min. Centrifuge a portion of this solution, and dilute the clear supernatant with Mobile phase to obtain a solution containing about 0.1 mg/mL of olanzapine. [NOTE-Agitation of the flask may be necessary before sonication to prevent Tablets from adhering to the flask, making disintegration and dissolution difficult.]
Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC
Detector: UV 260 nm
Column: 4.6-mm x 15-cm; 5-um packing L7
Flow rate: 1.5 mL/min
Injection volume: 20 uL
System suitability
Samples: System suitability solution and Standard solution
[NOTE-The relative retention times for olanzapine related compound A and olanzapine are 0.89 and
1.0, respectively.]
Suitability requirements
Resolution: NLT 2.0 between olanzapine and olanzapine related compound A, System suitability solution
Tailing factor: NMT 1.8, Standard solution
Relative standard deviation: NMT 2.0%, Standard solution
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of olanzapine (C17H20N4S) in the portion of Tablets taken:
Result= (Ru/Rs) x (Cs/Cu) x 100
Ru= peak response from the Sample solution
Rs= peak response from the Standard solution
Cs= concentration of USP Olanzapine RS in the Standard solution(mg/ml)
Cu= nominal concentration of olanzapine in the Sample solution (mg/ml)
Calculations:
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim
Limit: Olanzapine: 90%-110%of the labeled amount
ALTERNATE METHOD BY UV
Procedure:
Diluent: Acetonitrile : Water
50 : 50
Standard Solution:
Take 25 mg of Olanzapine WS dissolved in diluent and make up the volume to 50mL with diluent. Shake, and sonicate for 5 minutes to facilitate dissolution
Take 1 mL from standard stock solution and make up the volume to 50 mL with diluent.
Sample solution:
Take 5 gram of sample grind them to fine powder. Take compression weight of finally grinded powder equivalent to 25 mg of Olanzapine and dissolved in diluent and make up the volume to 50 with diluent. Shake by mechanical mean for 10 minutes to disperse and allow any insoluble matter to settle.
Pass a portion of the sample stock solution through a suitable filter of 0.45um pore size.
Transfer the 1 mL of filtrate to a 50 mL volumetric flask make up volume with diluent. Take reading at UV spectrophotometer at 260 nm using diluent as blank.
Calculations:
Sample Absorbance x Standard Concentration x Ave. Weight of Tablet x Potency
Standard Absorbance x Sample Concentration x Label Claim
Limit: Olanzapine: 90%-110%of the labeled amount
DISSOLUTION TEST:
USP Apparatus: USP Apparatus II Peddle
Medium: 900mL 0.1 N hydrochloric acid
Speed: 50 rpm
Time: 30 Minute
Medium Temperature: 37º ± 0.5º
Recommended Sampling Time: Olanzapine: 30 Minute
Mobile phase: 10 g/L of ammonium acetate in a mixture of methanol and water (2:3). Adjust with hydrochloric acid to a pH of 4.0.
Standard solution: (L/1000) mg/ml of USP Olanzapine RS in Medium, where L is the label claim in mg/Tablet. Transfer 5.0 ml of this solution to a tube, and add 2.0 ml of Mobile phase.
Sample solution: Pass a portion of the solution under test through a suitable filter of 0.45-um pore size. Transfer5.0 ml of the filtrate to a tube, and add 2.0 ml of Mobile phase.
Chromatographic system
(See Chromatography (621), System Suitability.)
Mode: LC
Detector: UV 260 nm
Column: 4.6-mm x 15-cm; 5um packing L10
Flow rate: 1.5 ml/min
Injection volume: 50 uL
System suitability
Sample: Standard solution
Suitability requirements
Relative standard deviation: NMT 2.0%
Analysis
Samples: Standard solution and Sample solution
Calculate the percentage of the labeled amount of olanzapine (C17H20N4S) dissolved:
Result= (ru/rs) x Cs x (V/L) x 100
ru= peak response from the Sample solution
rs= peak response from the Standard solution
Cs = concentration of USP Olanzapine RS in the Standard solution(mg/mL)
V = volume of Medium, 900 mL
L = label claim (mg/Tablet)
Tolerance:
The amount of drug dissolve in solution for each tablet is not less Than 80% (Q) of the amount stated on the label for olanzapine (C17H20N4S) at 30 minutes.
CONTENT UNIFORMITY TEST:
Proceed as directed in the assay.
Calculation of Acceptance Value (AV):
Limits:
L1= ≤ 15 (For 10 Unit)
L2= ≤ 25 (For 30 Unit)
General Formula = M-x̄ ±ks
Acceptability Constant = (k)
Standard Deviation (SD) = s
Number of Units = (n)
Reference Value = M
Mean of Individual Content = x̄
Disintegration Test:
Place the beaker filled with water into the beaker stand inside the bath and. Switch on the instrument, set the temperature at 37ºC± 2º C and wait till the temperature of the beaker reaches to the 37ºC± 2º C. Engage the basket on basket hook put the tablets in 6 tubes individually and place the discs then start the oscillations and timer. Note the disintegration time of all the six tablets.
Note the Disintegration time of 1st tablet to the last tablet.
Disintegration Time: NMT 15 minutes at 370C ± 20C
Acceptance criteria of disintegration for tablets:
If 1 or 2 tablet fail to disintegrate completely repeat the test on 12 additional tablets, not less than 16 of the total of 18 tablets tested disintegrate completely.
Hardness Test & Dimensions:
Perform the hardness test on 10 tablets and take the average. Power on the instrument and regulate zero adjustment and preset the ‘’HARDNESS’’ and “Thickness” mode. Place the tablet on the test plate, begin testing and read the hardness thickness and diameter. Clean the shattered tablet and print out test results, perform the test on 10 tablets and take the average.
Friability Test:
For tablets with a unit mass equal to or less than 650 mg, take a sample of whole tablets corresponding to 6.5 g. For tablets with a unit mass of more than 650 mg, take a sample of 10 whole tablets. The tablets should be carefully dedusted prior to testing. 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, and accurately weigh. Generally, the test is run once. If obviously cracked, cleaved, or broken tablets are present in the tablet sample after tumbling, the sample fails the test. If the results are doubtful 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.
% FRIABILITY= W1-W2/W1 x 100
Leak Test:
Take 06 blisters of tablet 03 filled and 03 empty. Dip these blisters in the bowl of leak test apparatus containing colored water. Create vacuum 250 mmHg and hold for one minute. Release vacuum and check the penetration of water inside the blisters. All blisters should be free of water.