A Critical Assessment of the Usp Dissolution Apparatus Suitability Test Criteria

Abstract

This report describes results of a survey conducted to assess the variability in drug release from the USP calibrators and its dependence on various deaeration methods. The calibrator data submitted by 33 laboratories, involved tests of 1659 sets (6 or 12 tablets/set) from four lots of prednisone and salicylic acid each, using apparatuses 1 & 2 run at 50 and 100 rpm. Overall variabilityranges for the individual sets, which met the USP dissolution apparatus Suitability Criteria, were 0.5-31.3% for prednisone/apparatus 1, 0-13.2% for salicylic acid/apparatus 1, 0.3-10.2% for prednisone/apparatus 2 and 0.7-20.2% for salicylic acid/apparatus 2. The results of this survey suggest that variability levels are dependent on apparatus/calibrator combination. Although deaeration of dissolution media tends to reduce the failures i.e. not meeting the Suitability Criteria, its effect on reducing the variability appears to be minimal. Among the various deaeration methods reported, degassing the media by a combination of heating with helium sparging or with filtering under vacuum tend to give the lowest failure rate. From our findings, a variability of up to 31% CV (coefficient of variation) in percent drug release for the calibrator can occur with the samples still meeting the USP criteria. However, if the apparatus/calibrator combination is taken into consideration with appropriate deaeration method, the maximum expected variability can be reduced to 10% or less. The results of this survey show that rather than an eight point dissolution calibration test criteria, a four point evaluation system i.e. testing non-disintegrating tablets with apparatus 1 and disintegrating tablets with apparatus 2 may provide sufficient information for system suitability. It is also recommended that a similar formulation/apparatus combination should be considered for drug products evaluation which might yield less variable results with an improved potentials of in vitro/in vivo correlations particularly for modifieddrug release products.