INFLUENCE OF THE CARRIER ON THE INTRINSIC RATE OF DISSOLUTION OF DIAZEPAM IN INTERACTIVE MIXTURES

The use of interactive mixtures of drugs adhering to the surface of ca rriers can promote drug dissolution. The mechanism of dissolution of s uch mixtures has been studied using the rotating-disc method under con ditions eliminating secondary influences such as carrier surface chara cteristics and drug particle aggregation. Levich plots were used to ch aracterize the dissolution behaviour. Diazepam-compactrol interactive mixtures had initial dissolution rates similar to that of pure diazepa m owing to the deposition of a continuous layer of diazepam on the dis c surface from the interactive mixture. Linear Levich plots were produ ced at all drug loadings and the presence of compactrol in the disc sl ightly enhanced dissolution rates. Dissolution rates for diazepam-emco mpress interactive mixtures were lower than those of pure diazepam. Th e Levich plots for these systems were non-linear with increasing negat ive curvature as the diazepam loading decreased. The rate of dissoluti on 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 cau sed surface retraction of the disc, enhancing the dissolution rate. Th e Levich plots showed an upward curvature due to turbulence. Linear Le vich plots for diazepam and other benzodiazepines and for diazepam-com pactrol interactive mixtures showed that their dissolution in pH 5 pho sphate buffer was diffusion-controlled. The Levich plots for diazepam- emcompress interactive mixtures were indicative of some interfacial co ntrol during dissolution, but the hypothesis of common ion precipitati on of dissolved carrier, calcium phosphate, onto the disc surface did not fully explain this effect.