In vitro evaluation of a controlled-release site-specific diisovaleryl tert-butalone chemical delivery system for the...

Cellulosic polymers such as cellulose acetate (CA), cellulose acetate butyrate (CAB), and hydroxypropyl methyl cellulose phthalate (HPMCP) and hydrogels (hydroxyethyl/hydroxypropyl acrylate and hydroxypropyl methacrylate monomers) were used to sustain/control the release of diisovaleryl tert-butalone, a novel site-specific chemical delivery system (CDS) for potential antiglaucoma treatment. Diisovaleryl tert-butalone was incorporated into cellulosic polymers by the method of "solution casting" and into hydrogels by the method of "impregnation." In vitro release-rate kinetics from these systems were studied using a closed sink kinetic model. The release rate of CDS from the polymers chosen followed first-order kinetics and the release was sustained for about 2-6 h. In the case of hydrogels a pronounced "burst release" was observed. Increasing the percentage of cross-linker in the linear monomers of the hydrogel was shown to sustain the release longer. When the diisovaleryl tert-butalone CDS was incorporated into one of the cellulosic polymers, cellulose acetate butyrate, as the CDS-beta-cyclodextrin [heptakis(2,6-di-O-methyl)-beta-cyclodextrin] inclusion complex, the release pattern approximated Higuchi's expression for a monolithic matrix system, where the amount of CDS released from the polymer was proportional to the square-root of time. Further, the stability of the CDS in the polymer was improved when it was dispersed in the polymer as the CDS-beta-cyclodextrin CD complex.