Bureau of Drug and Narcotic Mechanical Calibration Temperature control  Calibrated thermometer  ˚ C 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

USP Performance Verification Test (PVT) Bureau of Drug and Narcotic 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 Reference Standards for PVT Always use the current lot Follow the instructions on the label concerning storage and handling

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

Bureau of Drug and Narcotic Prednisone USP RS  Certificate  Label

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

Bureau of Drug and Narcotic Prednisone Tablets RS Certificate & Label

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

Bureau of Drug and Narcotic Prednisone Tablets RS Certificate

Bureau of Drug and Narcotic 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 0.45 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

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

Bureau of Drug and Narcotic Prednisone Tablets RS Futility Factor

Bureau of Drug and Narcotic 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) Steps for PVT

Bureau of Drug and Narcotic 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 Steps for PVT

Bureau of Drug and Narcotic Search for PVT calculation tool Select “Begin using the tool” PVT Calculation Toolkit

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

Bureau of Drug and Narcotic PVT Calculation Toolkit

Bureau of Drug and Narcotic Select apparatus PVT Calculation Toolkit

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

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

Bureau of Drug and Narcotic Submit data PVT Calculation Toolkit

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

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

Bureau of Drug and Narcotic Submit data PVT Calculation Toolkit

Bureau of Drug and Narcotic Result & Report PVT Calculation Toolkit

Recommendations for PVT Bureau of Drug and Narcotic - 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

Prednisone Tablets RS Bureau of Drug and Narcotic  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

Sources of factors influence dissolution Bureau of Drug and Narcotic Laboratory environment Medium FiltrationQuantitative method Note: instrument and analyst are qualified

Vibration Bureau of Drug and Narcotic  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

Laboratory Environment Bureau of Drug and Narcotic  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

Medium Bureau of Drug and Narcotic  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

Filtration Bureau of Drug and Narcotic  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

Filtration Bureau of Drug and Narcotic  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

When to perform PVT ? Bureau of Drug and Narcotic  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 Bangkok Chemart Ltd., Part Where to buy USP RS ?

Bureau of Drug and Narcotic