Mechanical Calibration

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Ernest Butler
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1 Mechanical Calibration Distance between the inside bottom of the vessel and the bottom of the basket or paddle is maintained at mm during the test use a spacing gauge or ball Temperature control Calibrated thermometer C

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.

3 Reference Standards for PVT Always use the current lot Follow the instructions on the label concerning storage and handling

4 Prednisone USP RS Check Current lot Validity

5 Prednisone USP RS Certificate Label

6 Prednisone Tablets RS Check Current lot Validity

7 Prednisone Tablets RS Certificate & Label

8 Prednisone Tablets RS Store in a dry place. Store at controlled room temperature Not exceeding 25 ºC

9 Prednisone Tablets RS Certificate

10 Prednisone Tablets RS Dissolution medium: - Water: DI - Preparing the medium Deaeration

USP Deaeration Technique - Heat water while stirring gently to about 41 45 C -Filter under vacuum through 0.

11 USP Deaeration Technique - Heat water while stirring gently to about 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)

13 Single - Stage Test Two Stage Test Prednisone Tablets RS Result: GM %CV

14 Prednisone Tablets RS Futility Factor

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 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)

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

17 PVT Calculation Toolkit Search for PVT calculation tool Select Begin using the tool

18 PVT Calculation Toolkit

19 PVT Calculation Toolkit

20 PVT Calculation Toolkit

21 PVT Calculation Toolkit

22 PVT Calculation Toolkit

23 PVT Calculation Toolkit

24 PVT Calculation Toolkit

25 PVT Calculation Toolkit Data of 6 vessels with 3 decimals

26 PVT Calculation Toolkit Submit data

27 PVT Calculation Toolkit Result & Report

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

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

30 Sources of factors influence dissolution Laboratory environment Medium Filtration Quantitative method Note: instrument and analyst are qualified

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

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

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

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

35 Precautions: Filtration - 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

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.

37 Where to buy USP RS? Bangkok Chemart Ltd., Part

Tablet Dissolution Testing

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