Release characterization of dimenhydrinate from an eroding and swelling matrix: selection of appropriate dissolution apparatus.

ABSTRACT

The objective of this study was to evaluate the effect of various hydrodynamic conditions on drug release from an eroding and gel forming matrix. For this purpose, dimenhydrinate was formulated with hydroxypropyl methyl cellulose and polyethylene oxide into matrix tablets and the drug release in deionized water was evaluated spectrophotometrically, using multiple dissolution methods, namely, compendial USP 27-apparatus I-III, and a modified apparatus II (paddle over mesh). Various hydrodynamic conditions were examined at the agitation rates of 50 and 100 rpm for apparatus I and II, and 5 and 8 dpm for apparatus III. Similarity and difference factors were calculated using compendial apparatus II release data as reference. Among the methods, apparatus I showed the slowest initial release, while the release from apparatus III at 8 dpm was the highest among the methods. This was further compared via the dissolution half-times and calculation of the average release rate for each method. Based on the analysis of difference and similarity factors (f(1) and f(2)), the study clearly demonstrates the significance of hydrodynamics and the choice of a dissolution method and their respective effect on overall release profiles when erodible and swellable matrix systems are involved. Full surface exposure with insertion of mesh device in apparatus II may provide more realistic conditions especially when release data are to be used in developing IVIVCs.