Method validation for filters used in Dissolution

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This article contains protocol for method validation for filters used in Dissolution method.

Method validation for filters used in Dissolution Method

Approval for protocol of Method validation for filters used in Dissolution method

  Designation Name Signature Date
Prepared By Executive QC      
Reviewed By Dy. Manager QC  

 

    
Head QC  

 

    
Approved By Head QA      

Protocol Content for Method validation for filters used in Dissolution Method :

Sr. No  

Contents Name

 
1.0 Purpose
2.0 Scope
3.0 Reference
4.0 Site of the Study
5.0 Responsibility
6.0 Materials and instrument
7.0 Validation Procedure
8.0 Acceptance Criteria
9.0 Results
10.0 Conclusion
11.0 Attachments

   

  1. Purpose :

To validate the analytical test method for filters used in Dissolution method of Azithromycin in Azithromycin tablets USP 500 mg

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  1. Scope :

This method validation study is applicable for Dissolution of Azithromycin in Azithromycin tablets USP 500 mg.

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  1. Reference :

Analytical Method Validation SOP

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  1. Site of the study :

NA

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  1. Responsibility :

Analyst / Executive / Head Quality Control /Quality Assurance.

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6. Materials, Columns, STP and Instrument used for Method validation for filters used in Dissolution:

Instruments:

Sr. no Instrument Name Make
1 Analytical Balance Mettler Toledo
2 Analytical Balance Mettler Toledo
3 pH Meter LABINDIA
4 HPLC SHIMADZU
5 Dissolution Apparatus LABINDIA

Reagent / Chemicals :

Sr. No Reagents/Chemicals Grade
     1 Water Purified Water
2 Dibasic Potassium Phosphate AR  Grade
3 Monobasic Potassium Phosphate AR  Grade
4 Sodium Hydroxide AR  Grade
5 1-Octanesulfonate AR  Grade
6 Phosphoric acid AR  Grade
7 Acetonitrile HPLC  Grade
8 Methanol HPLC  Grade

Working Standard/Impurity Standard

Sr. No. Standard
1 Azithromycin Working Standard

 STP

Sr. No. STP NO. Version

HPLC Column

Sr. No. Column Description Column No.
1 4.6 mm x 15 cm ; 5-µm packing L1 –

  1. Validation procedure or Method validation for filters used in Dissolution :

  •  Perform the validation by following the procedure designed under following validation parameters.
  • Chromatographic conditions, Mobile phase, diluents, System suitability preparation and Standard preparation shall be prepared according to STP no. T60100, Version – 07.
  • Injection sequence shall be modified when two or more parameters are merged together while performing validation.

Validation Parameters for Method validation for filters used in Dissolution  :

  1. Efficiency
  2. Leachability
  3. Adsorbance

 

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  1. Acceptance criteria:

   System suitability and Acceptance criteria for above validation parameters are specified in STP and individual parameters respectively.

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  1. Results:

1) Observations and results shall be recorded in individual method validation test data sheet and excel sheet.

2)  Summarize the findings of the  Method validation for filters used in Dissolution study to draw Conclusion.

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  1. Conclusion:

                   Based on the interpretation of the results in method validation summary, draw the conclusion.

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  • Attachments:

  1) Annexure I: Method of Analysis for method validation for filters used in Dissolution

Procedural Part for Validation Parameters for Method validation for filters used in Dissolution :

Efficiency :

  • Placebo preparation:

Transfer 900 mL of dissolution medium in the dissolution vessel carefully and allow the medium to equilibrate to a temperature of 37±0.5°C. weigh and add placebo equivalent to one tablet in one of dissolution vessel and operate the apparatus at 75 RPM for specified time interval. Withdraw 10 ml of the sample from dissolution vessel. Further, filter the dissolution solution through nylon membrane filter 0.45µm, PTFE membrane filter 0.45 µm and Whatman filter paper separately to get clear solution. Dilute 5 mL of the above test solution in to 10 ml volumetric flasks, dilute to volume with diluent and Mix well.

  • Sample solution Efficiency test:

Transfer 900 mL of dissolution medium in the dissolution vessel carefully and allow the medium to equilibrate to a temperature of 37±0.5°C. weigh and add 250 mg of Azithromycin API and placebo equivalent to one tablet in one of dissolution vessel and operate the apparatus at 75 RPM for specified time interval.

Withdraw 10 ml of the sample from dissolution vessel. Further, filter the dissolution solution through nylon membrane filter 0.45µm, PTFE membrane filter 0.45 µm and Whatman filter paper separately to get clear solution.

Prepare sample solution with three procedures after filteration as follows,

  1. Analyze without sonication.
  2. Ultrasonicate for 5 minutes.
  3. Ultrasonicate for 10 minutes.

Further, dilute 5 mL of each of the above sample solution in to 10 ml volumetric flasks, dilute to volume with diluent and Mix well.

  • Injection Sequence:

Sr. No. Solution No. of Injections
1. Blank 1
2. Standard solution_A 1
3. Standard solution_B 6
4. Blank 1
5. Placebo solution_ nylon membrane filter 0.45µm 1
6. Placebo solution_ PTFE membrane filter 0.45µm 1
7. Placebo solution_ Whatman filter paper 1
8. Sample solution_ nylon 0.45µm_Initial 1
9. Sample solution_ nylon 0.45µm_5 min. 1
10. Sample solution_ nylon 0.45µm_10 min. 1
11. Sample solution_ PTFE 0.45µm_Initial 1
12. Sample solution_ PTFE 0.45µm_5 min. 1
13. Sample solution_ PTFE 0.45µm_10 min. 1
14. Bracketing standard solution 1
15. Sample solution_ Whatman filter_Initial 1
16. Sample solution_ Whatman filter_5 min. 1
17. Sample solution_ Whatman filter_10 min. 1
18. Bracketing standard solution 1

  •  System suitability criteria:

Sr. No. System suitability parameter Acceptance criteria
1. % RSD The % RSD for the six replicate injections of the standard solution should be not more than 2.0

 
2. Tailing Factor Tailing factor for Azithromycin peak should be not more than 2.0

 
3. Similarity factor The Similarity factor between standard solutions should be 0.98 to 1.02.

 

  • Acceptance criteria:

Sr. No. Parameter Acceptance criteria
1. % Difference of drug dissolved % difference should not be more than 2.0% between initial and ultra sonicated sample solutions.

Leachability :

  • Preparation of blank solution:

Transfer 900 mL of dissolution medium in the dissolution vessel carefully and allow the medium to equilibrate to a temperature of 37±0.5°C. Operate the apparatus at 75 RPM for specified time interval. Withdraw 10 ml of the sample from dissolution vessel. Further, filter the dissolution solution through nylon membrane filter 0.45µm, PTFE membrane filter 0.45 µm and Whatman filter paper separately to get clear solution. Dilute 5 mL of the above test solution in to 10 ml volumetric flasks, dilute to volume with diluent and Mix well.

  • Preparation of working standard solution:

Weigh 25 mg of Azithromycin working Standard in 100 ml volumetric flask, add 70 mL of dissolution medium and dissolve. Dilute to volume with dissolution medium. Further, dilute 5 mL of the above test solution in to 10 ml volumetric flasks, dilute to volume with diluent and mix well.

  • Injection Sequence:

Sr. No. Solution No. of Injections
1. Blank 1
2. Standard solution_A 1
3. Standard solution_B 6
4. Blank 1
5. Blank solution_nylon membrane filter 0.45µm 1
6. Blank solution_PTFE membrane filter 0.45µm 1
7. Blank solution_Whatman filter paper 1
8. Working standard solution_Unfiltered 3
9. Bracketing standard solution 1

  • System suitability criteria:

Sr. No. System suitability parameter Acceptance criteria
1. % RSD The % RSD for the six replicate injections of the standard solution should be not more than 2.0

 
2. Tailing Factor Tailing factor for Azithromycin peak should be not more than 2.0

 
3. Similarity factor The Similarity factor between standard solutions should be 0.98 to 1.02.

  • Acceptance criteria:

Sr. No. Parameter Acceptance criteria
1. % response for blank solution The % response of blank solution filtered through filters should not be more than 0.5 % of the mean response of working standard solution.

 Absorbance:

  • Recovery solution:

Transfer 900 mL of dissolution medium in the dissolution vessel carefully and allow the medium to equilibrate to a temperature of 37±0.5°C. weigh and add 250 mg of Azithromycin API and placebo equivalent to one tablet in one of dissolution vessel and operate the apparatus at 75 RPM for specified time interval.

  • Unfiltered solution:

Withdraw 10 ml of the sample from dissolution vessel. Further, dilute 5 mL of this solution to 10 mL volumetric flask with diluent.

  • Filtered solution:

Withdraw 10 ml of the sample from dissolution vessel in. Further, filter the dissolution solution through nylon membrane filter 0.45µm, PTFE membrane filter 0.45 µm and Whatman filter paper separately to get clear solution as per below table.

Sr. No. Volume of Solution to be filtered in mL Diluted to volume with diluent in mL
1 1 2
2 2 4
3 3 6
4 4 8
5 5 10
6 6 12
7 7 14
8 8 16
9 9 18
10 10 20

  • Injection Sequence:

Sr. No. Solution No. of Injections
1. Blank 1
2. Standard solution_A 1
3. Standard solution_B 6
4. Unfiltered solution 3
5. Filtered solution_1 mL_nylon filter 0.45µm 1
6. Filtered solution_2 mL_nylon filter 0.45µm 1
7. Filtered solution_3 mL_nylon filter 0.45µm 1
8. Bracketing standard solution 1
9. Filtered solution_4 mL_nylon filter 0.45µm 1
10. Filtered solution_5 mL_nylon filter 0.45µm 1
11. Filtered solution_6 mL_nylon filter 0.45µm 1
12. Filtered solution_7 mL_nylon filter 0.45µm 1
13. Filtered solution_8 mL_nylon filter 0.45µm 1
14. Filtered solution_9 mL_nylon filter 0.45µm 1
15. Bracketing standard solution 1
16. Filtered solution_10 mL_nylon filter 0.45µm 1
17. Filtered solution_1 mL_PTFE filter 0.45µm 1
18. Filtered solution_2 mL_PTFE filter 0.45µm 1
19. Filtered solution_3 mL_PTFE filter 0.45µm 1
20. Filtered solution_4 mL_PTFE filter 0.45µm 1
21. Filtered solution_5 mL_PTFE filter 0.45µm 1
22. Bracketing standard solution 1
23. Filtered solution_6 mL_PTFE filter 0.45µm 1
24. Filtered solution_7 mL_PTFE filter 0.45µm 1
25. Filtered solution_8 mL_PTFE filter 0.45µm 1
26. Filtered solution_9 mL_PTFE filter 0.45µm 1
27. Filtered solution_10 mL_PTFE filter 0.45µm 1
28. Bracketing standard solution 1
29. Filtered solution_1 mL_Whatman filter 1
30. Filtered solution_2 mL_Whatman filter 1
31. Filtered solution_3 mL_Whatman filter 1
32. Filtered solution_4 mL_Whatman filter 1
33. Filtered solution_5 mL_Whatman filter 1
34. Filtered solution_6 mL_Whatman filter 1
35. Bracketing standard solution 1
36. Filtered solution_7 mL_Whatman filter 1
37. Filtered solution_8 mL_Whatman filter 1
38. Filtered solution_9 mL_Whatman filter 1
39. Filtered solution_10 mL_Whatman filter 1
40. Bracketing standard solution 1

 

  • Calculation:

 

Area response of filtered solution

% Recovery =     —————————————————– x100

Mean area response of unfiltered solution

 

  • System suitability criteria:
Sr. No. System suitability parameter Acceptance criteria
4. % RSD The % RSD for the six replicate injections of the standard solution should be not more than 2.0

 
5. Tailing Factor Tailing factor for Azithromycin peak should be not more than 2.0

 
6. Similarity factor The Similarity factor between standard solutions should be 0.98 to 1.02.

  • Acceptance Criteria:

Sr. No. Parameter Acceptance criteria
1. % Recovery % Recovery should be between 98.0% and 102.0 % for discard volume.

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