Temperature, pH and agitation rate as dissolution test discriminators of zofenopril calcium tablets

Abstract Comparative in vitro dissolution studies were performed on several tablet batches of zofenopril calcium, an ACE inhibitor, to determine if they could be differentiated on the basis of their release rates. The samples included six batches produced at Site I and one batch produced at Site 2. Using regular dissolution conditions (USP paddle method at a 50-rpm agitation speed in phosphate buffer, pH 7.5, at 37°C), release rates of all the tablet batches were similar. By independently altering one of the dissolution test parameters, either a lower pH or a slower agitation rate, discrimination between the Site I and Site 2 tablets was enhanced. Discrimination was only slightly enhanced when a lower dissolution medium temperature was used. Tablets made from different polymorphs of zofenopril calcium could not be differentiated by their dissolution profiles, even with the more discriminating conditions. The dissolution profiles of certain other zofenopril calcium tablets (including film-coated vs uncoated tablets, and tablets made with micronized vs unmicronized drug particles) were indistinguishable using a 50-rpm agitation rate, but they could be clearly differentiated using a 40-rpm agitation rate.