Mechanical Calibration

1. Mechanical Calibration • Distance between the inside bottom of the vessel • and the bottom of the basket or paddle is maintained • at 25 + 2 mm during the test • use a spacing gauge or ball • Temperature control • Calibrated thermometer • 37 + 0.5 ˚C Bureau of Drug and Narcotic

2. USP Performance Verification Test (PVT) • Provide experimental proof that the dissolution test • assembly is suitable for dissolution testing • Confirms the acceptable operation of the equipment • The result must conform to range given in the • certificate for the specification lot of reference material. • PVT is a prerequisite for a proper performance • qualification of the dissolution assembly. Bureau of Drug and Narcotic

3. Reference Standards for PVT Bureau of Drug and Narcotic

4. Prednisone USP RS • Check • Current lot • Validity Bureau of Drug and Narcotic

5. Prednisone USP RS • Certificate • Label Bureau of Drug and Narcotic

6. Prednisone Tablets RS • Check • Current lot • Validity Bureau of Drug and Narcotic

7. Prednisone Tablets RS Certificate & Label Bureau of Drug and Narcotic

8. Prednisone Tablets RS • Store in a dry place. • Store at controlled room temperature • Not exceeding 25 ºC Bureau of Drug and Narcotic

9. Prednisone Tablets RS Certificate Bureau of Drug and Narcotic

10. Prednisone Tablets RS • Dissolution medium: • Water: DI • Preparing the medium • “Deaeration” Bureau of Drug and Narcotic

11. USP Deaeration Technique • Heat water • while stirring gently • to about 41 – 45 C • Filter under vacuum • through 0.45 um • porosity filter into • a filtering flask with • a stirring device • Seal the flask, • continue to apply vacuum • while stirring for 5 min • Vacuum should be • < 100 mbar • Temperature of medium • not fall below 37 C

12. Prednisone Tablets RS • Procedure: • 499 g of deaerated water • (500 ml) • 37 C • each apparatus at 50-rpm • 30 minutes • uv at 242 nm • alcohol < 5% of total volume • of standard solution (If used) Bureau of Drug and Narcotic

13. Prednisone Tablets RS • Single - Stage Test • Two – Stage Test • Result: • GM • %CV Bureau of Drug and Narcotic

14. Prednisone Tablets RS Futility Factor Bureau of Drug and Narcotic

15. Steps for PVT • Deaerated water • Weight and carefully introduce dissolution medium • to the vessel 499 ml (500 g) • Allow media in each vessel to reach 37 + 0.5 ºC • and use immediately. • Always handle tablets with • - gloves (not cotton) • - forceps or tweezers which will not scratch or • damage the surface of the tablets • Examine all 6 tablets, do not use chipped, cracked or • Capped tablets • No need to weigh Tablets RS beforehand • (Weight is for information and investigation purposes) Bureau of Drug and Narcotic

16. Steps for PVT • Prepare to drop tablets. • For Apparatus 2 Paddle • - Drop tablets into non-rotating apparatus • - Tablets must settle to the bottom of the vessel • before rotation of the shaft begins. • Record time • Samples should remain at the bottom center of the vessel • Visually inspect and record any unusual observations • Withdraw sample at 30 minutes + 36 seconds (+2%) • and filter immediately • Measure the amount of prednisone dissolved at • 242 nm in comparison with a solution of known • concentration of USP Prednisone RS • Calculation and conclusion Bureau of Drug and Narcotic

17. PVT Calculation Toolkit www.usp.org Search for PVT calculation tool Select “Begin using the tool” Bureau of Drug and Narcotic

18. PVT Calculation Toolkit Select prednisone tablet RS lot Bureau of Drug and Narcotic

19. PVT Calculation Toolkit Bureau of Drug and Narcotic

20. PVT Calculation Toolkit Select apparatus Bureau of Drug and Narcotic

21. PVT Calculation Toolkit Select configuration of dissolution Bureau of Drug and Narcotic

22. PVT Calculation Toolkit Select testing procedure 1-stage or 2-stage Bureau of Drug and Narcotic

23. PVT Calculation Toolkit Submit data Bureau of Drug and Narcotic

24. PVT Calculation Toolkit Information - Date - Operator - ID - Note Bureau of Drug and Narcotic

25. PVT Calculation Toolkit Data of 6 vessels with 3 decimals Bureau of Drug and Narcotic

26. PVT Calculation Toolkit Submit data Bureau of Drug and Narcotic

27. PVT Calculation Toolkit Result & Report Bureau of Drug and Narcotic

28. Recommendations for PVT • Designated vessels and shaft for each position • in dissolution instrument • Rigorous mechanical calibration • Proper deaeration of dissolution medium • Test should be started as soon as possible • after media deaeration • Filter samples immediately after withdrawing • samples from each vessel Bureau of Drug and Narcotic

29. Prednisone Tablets RS • Tablet should be stored in original container, • according to description on label • Remove tablets from package immediately • prior to testing • Do not put tablet RS next to water bath • while waiting for bath to equilibrate • Avoid exposure to excess humidity • Prednisone Tablets RS will give low results • Do not dry Prednisone Tablets RS in an oven • No need to weigh Tablets RS beforehand Bureau of Drug and Narcotic

30. Sources of factors influence dissolution Note: instrument and analyst are qualified Bureau of Drug and Narcotic

31. Vibration • USP specification: • “ No part of the assembly, including the environment • in which the assembly is placed, contributes significant • motion, agitation, or vibration beyond that due to the • smoothly rotating stirring element.” • Source of vibration: • * Apparatus • - Tension or dirt on the drive chain or belt • - Worn parts • - Alignment of belt guide plates • - Surging of individual spindles • - Turbulence in the water bath Bureau of Drug and Narcotic

32. Laboratory Environment • Has anything changed in the lab environment? • - New equipment added to the immediate area • - Other changes (e.g. construction) • Vibration transfer • - Be careful how many testers put on the same bench • - Is bench suitable? • - What else is on the bench or nearby? • shaker, mixer, centrifuge • - consider use of vibration damping pads Bureau of Drug and Narcotic

33. Medium • Using deaerated media • - use immediately after deaeration • - transfer media carefully to minimize re-aeration • of the media • Air bubbles can attach to particles • - decreasing dissolution by reducing surface area • - Increasing dissolution by • # lifting and moving particles • # bubble clogging the meshes of the basket • and retaining particles in a zone of higher • shear stress compare to the vessel bottom Bureau of Drug and Narcotic

34. Filtration • Removal of undissolved particles • i.e. drug or excipients in the sample solution • Filtration should occur concomitantly with or • immediately after sampling • Unfiltered sample can continue drug dissolution • before filtration • Use Individual, clean syringes and filters • for sampling each vessel, each time Bureau of Drug and Narcotic

35. Filtration • Precautions: • - Prewetting may be necessary • - Adsorption of the drug onto the filter has to be • evaluated • - Chemical compatibility and extractable impurities • should be considered by the selection of • the proper (inert) filter material • - Important to perform filter check/validation • *** PVDF membrane filter is recommended for PVT Bureau of Drug and Narcotic

36. When to perform PVT ? • Installation of new apparatus • Movement or relocation of apparatus • Equipment maintenance • - Adjustment of drive mechanism • - Replacement of drive belt • - Replacement of circulator • - Replacement of vessels, baskets, paddle etc • Routine test schedule • If only one apparatus, basket or paddle, is used, • then only that apparatus needs to be tested. Bureau of Drug and Narcotic

37. Where to buy USP RS ? Bangkok Chemart Ltd., Part. www.bangkokchemart.com sam.bcm@gmail.com 02 720 9557 - 9 Bureau of Drug and Narcotic

38. Bureau of Drug and Narcotic