A CRITICAL-ASSESSMENT OF THE USP DISSOLUTION APPARATUS SUITABILITY TEST CRITERIA

This report describes results of a survey conducted to assess the vari ability in drug release from the USP calibrators and its dependence on various deaeration methods. The calibrator data submitted by 33 labor atories, involved tests of 1659 sets (6 or 12 tablets/set) from four l ots of prednisone and salicylic acid each, using apparatuses 1 & 2 run at 50 and 100 rpm. Overall variability-ranges 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/appara tus 1, 0.3-10.2% for prednisone/apparatus 2 and 0.7-20.2% for salicyli c acid/apparatus 2. The results of this survey suggest that variabilit y levels are dependent on apparatus/calibrator combination. Although d eaeration of dissolution media tends to reduce the failures i.e. not m eeting the Suitability Criteria, its effect on reducing the variabilit y appears to be minimal. Among the various deaeration methods reported , de-gassing the media by a combination of heating with helium spargin g or with filtering under vacuum tend to give the lowest failure rate. From our findings, a variability of up to 31% CV (coefficient of vari ation) in percent drug release for the calibrator can occur with the s amples still meeting the USP criteria. However, if the apparatus/calib rator combination is taken into consideration with appropriate deaerat ion 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 disintegr ating 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 evaluatio n which might yield less variable results with an improved potentials of in vitro/in vivo correlations particularly for modified-drug releas e products.