STEREOSPECIFIC DETERMINATION OF THE IN-VITRO DISSOLUTION OF MODIFIED RELEASE FORMULATIONS OF (+ -)-VERAPAMIL/

The determination of the in vitro dissolution profiles of three differ ent modified-release formulations of (+/-)-verapamil were determined a nd compared to a reference (Calan SR). The determination of (+/-)-vera pamil utilized a microwave-facilitated derivatization reaction with an enantiomerically pure reagent followed by measurement of drug by reve rsed-phase high-performance liquid chromatography (HPLC). The dissolut ion profile of each of the four modified-release formulations was foll owed for the first hour in simulated gastric fluid (pH 1.2) and then i n simulated intestinal fluid (pH 7.5) for up to a total of 12 h. The r esulting dissolution profiles of each modified-release formulation sug gested that only one of the three test formulations had a similar diss olution to the Calan SR reference. Interestingly, the (S:R)-enantiomer ratios of two of the test products were significantly different from unity, and the third test product was also significantly different fro m unity if 4 out of 5 outliers were omitted. It is suggested that diss olution testing of modified-release formulations containing chiral act ive ingredients must be stereospecific in order to discern whether a d rug-excipient interaction occurs. Additionally, it may be suggested th at dissolution techniques relying more upon diffusion of medium throug h the tablet matrix, rather than erosion of the tablet, may accentuate enantiomeric differences in release rates. (C) 1993 Wiley-Liss, Inc.