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Olanzapine 10mg Tablet Standard Analytical Procedure
Reference: United States Pharmacopoeia
APPROVAL BLOCK
| Title | Designation | Signature/Date |
| Written By: | Quality Control Analyst | |
| Reviewed By: | Quality Control Manager | |
| Verified By: | Quality Assurance Incharge | |
| Approved By: | Technical Operation Director |
Distribution List
| Sr. # | Department | New revision # | Retrieval Revision # | Signature & Date |
DOCUMENT REVISION CONTROL
| Rev. # | Date | Initiated By | Page # | Nature of Amendment | Done By |
1.0 PURPOSE
2.0 SCOPE
3.0 RESPONSIBILITY
4.0 REFERENCE
5.0 MATERIAL AND EQIUPMENT
6.0 PROCEDURE
7.0 RISK ANALYSIS
1.0 PURPOSE:
To describe the procedure for analysis at the in-process and finished stage of Olanzapine 10mg Tablet.
2.0 SCOPE:
This SAP gives detailed outline for the finished product analysis of Olanzapine 10mg Tablet and will cover In process testing activities on physical, chemical & instrumental basis.
3.0 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.
4.0 REFERENCE:
USP 44 NF 39
5.0 MATERIAL AND EQIUPMENT:
- HPLC
- 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
6.0 PROCEDURE:
6.1 FINAL MIX
6.1.1 Description:
A white to off white granular powder.
6.1.1.1 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.
6.1.2 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.
6.1.3 Loss on Drying: (By Moisture Analyzer)
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.
6.1.4 Assay: (Limit: 90%-110%) Compression Weight of Powder/Tablet:…. mg /tablet
6.1.4.1 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 (NLT 5), 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
6.2 CORE TABLET
6.2.1 Description:
White, round, biconvex, bisect, core, tablet.
6.2.2 Compression weight/Tablet: …. mg ± 7.50%
6.2.3 Uniformity of Dosage Units: (By Weight Variation)
Weigh 20 tablets individually and calculate the average weight as:
Average weight = (Weight Of 20 Tablets)/20
Weigh all these tablets individually and mark among these weights maximum (WMax) & minimum (WMin) weight tablets. Calculate the maximum and minimum variation in percent as:
Maximum% age variation = ((WMax) – (WAvg.))/WAvg×100
Minimum % age variation ((WMin) – (WAvg.))/WAvg×100
Standard Limit: ± 7.50%
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.
Hardness Standard Limit: Not more than 10.00 Kg
Thickness Standard Limit: …. mm + 0.30 mm
Length/Diameter Standard Limit: ….. mm ± 0.20 mm
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 x 100/W1
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
6.3 FILM COATING
6.3.1 Description:
A film coated ……. color, round, biconvex bisect tablet
Weight/Tablet:…. mg ± 7.50%
6.3.2 Uniformity of Dosage Units: (By Weight Variation) Proceed as directed in Compression stage Standard Limit: ± 7.50%
6.3.3 Hardness Test & Dimensions:
Proceed as directed in Compression stage
Hardness Standard Limit: Not more than 10.00 Kg
Thickness Standard Limit: ….. mm ± 0.30 mm
Length/Diameter Standard Limit: ….. mm ± 0.20 mm
6.3.4 Disintegration Test:
Proceed as directed in Compression stage
Disintegration Time: NMT 30 minutes at 370C ± 20C
6.4 Blister
6.4.1 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.
6.5 FINISHED PRODUCT TEST:
6.5.1 Definition:
Olanzapine 10 mg Tablet contain 90.0%-110.0% of the labeled amount of Olanzapine.
Label Claim: Olanzapine 10 mg per Tablet
6.5.2 Description:
A film coated sky blue color round biconvex, one side bisect tablet alu alu blister with leaflet pack in unit carton.
Weight/Tablet: 246 mg ± 7.50%
6.5.3 Uniformity of Dosage Units: (By Weight Variation)
Proceed as directed in Compression stage
Standard Limit: ± 7.50%
6.5.4 Hardness Test & Dimensions:
Proceed as directed in Compression stage
Hardness Standard Limit: Not more than 10.00 Kg
Thickness Standard Limit: 4.00 mm + 0.30 mm
Length/Diameter Standard Limit: 8.50 mm ± 0.20 mm
6.5.5 Disintegration Test:
Proceed as directed in Compression stage
6.5.5.1 Disintegration Time: NMT 30 minutes at 370C ± 20C
6.5.6 ASSAY BY HPLC:
6.5.6.1 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 (NLT 5), 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
Average Sample AUC x Standard Concentration x Ave. Weight of Tablet x Potency
Average Standard AUC x Sample Concentration x Label Claim x Factor
Limit: Olanzapine: 90%-110%of the labeled amount
6.5.7 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. Transfer 5.0 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.
6.5.8 CONTENT UNIFORMITY TEST:
6.5.8.1 Proceed as directed in the assay.
6.5.8.2 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
| Case 1 | Case 2 |
| Applied when T ≤ 101.5 | Applied when T ≥ 101.5 |
| If number of units=10 then k value = 2.4; If no. of units=30 then k=2.0 | If number of units=10 then k value = 2.4; If n=30 then k=2.0 |
| T= Label claim percent at time of manufacturing | T= Label claim percent at time of manufacturing |
| If average value 98.5% ≤ x̄ ≤ 101.5% then M=x̄; (AV=ks) | If average value 98.5% ≤ x̄ ≤ T then M=x̄; (AV=ks) |
| If x̄ < 98.5% then M=98.5%; (AV=98.5- x̄+ ks) | If x̄ < 98.5% then M=98.5%; (AV=98.5- x̄+ ks) |
| If x̄ > 101.5% then M=101.5%; (AV= x̄-101.5+ ks) | If x̄ > T then M=T; (AV= x̄-T+ ks) |
Formula’s:
1) If average value 98.5% ≤ x̄ ≤ 101.5% then M=x̄; (AV=ks)
2) If x̄ < 98.5% then M=98.5%; (AV=98.5- x̄+ ks)
3) If x̄ > 101.5% then M=101.5%; (AV= x̄-101.5+ ks
6.5.9 PACKAGING SPECIFICATIONS:
6.5.9.1 Primary Packaging:
Olanzapine 10 mg Tablet packed in printed Aluminium foil 250mm with blister pack of Alu Alu foil 250mm, in unit carton.
6.5.9.2 Secondary Packaging:
Standard unit pack capacity to hold alu alu blister tablets with leaflet.
6.5.10 PACKAGING AND STORAGE:
Preserve in tight, light-resistant containers, and store at controlled room temperature.
7.0 RISK ANALYSIS:
EVIDENCES OF RECORDS & REFERENCES: USP44, NF39
Certificate of Analysis Finished Product
Finished Product QC Number log
Finished Product Batch Analysis Sheet
Finished Product Specification
Product Release Sticker
Raw Data Calculation Sheets