Influence of the Carrier on the Intrinsic Rate of Dissolution of Diazepam in Interactive Mixtures

Abstract

Abstract The use of interactive mixtures of drugs adhering to the surface of carriers can promote drug dissolution. The mechanism of dissolution of such mixtures has been studied using the rotating-disc method under conditions eliminating secondary influences such as carrier surface characteristics and drug particle aggregation. Levich plots were used to characterize the dissolution behaviour. Diazepam-compactrol interactive mixtures had initial dissolution rates similar to that of pure diazepam owing to the deposition of a continuous layer of diazepam on the disc surface from the interactive mixture. Linear Levich plots were produced at all drug loadings and the presence of compactrol in the disc slightly enhanced dissolution rates. Dissolution rates for diazepam-emcompress interactive mixtures were lower than those of pure diazepam. The Levich plots for these systems were non-linear with increasing negative curvature as the diazepam loading decreased. The rate of dissolution of diazepam in the lactose interactive mixture was markedly higher than that of pure diazepam, but high diazepam loadings in the lactose mixtures inhibited diazepam dissolution. Rapid carrier dissolution caused surface retraction of the disc, enhancing the dissolution rate. The Levich plots showed an upward curvature due to turbulence. Linear Levich plots for diazepam and other benzodiazepines and for diazepam-compactrol interactive mixtures showed that their dissolution in pH 5 phosphate buffer was diffusion-controlled. The Levich plots for diazepam-emcompress interactive mixtures were indicative of some interfacial control during dissolution, but the hypothesis of common ion precipitation of dissolved carrier, calcium phosphate, onto the disc surface did not fully explain this effect.