In vitro evaluation of a controlled-release site-specific diisovaleryl tert-butalone chemical delivery system for the eye.
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.
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Center for Drug Discovery, College of Pharmacy, J. Hillis Miller Health Center, University of Florida, Gainesville 32610.
Bodor
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D002482:Cellulose; D003692:Delayed-Action Preparations; D004355:Drug Stability; D005079:Excipients; D005901:Glaucoma / Q000188:drug therapy*; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D009883:Ophthalmic Solutions; D011092:Polyethylene Glycols; D014631:Valerates / Q000008:administration & dosage* / Q000032:analysis
D003692:Delayed-Action Preparations; D005079:Excipients; D009883:Ophthalmic Solutions; D014631:Valerates; C087642:diisovaleryl tert-butalone; D020136:Hydrogel, Polyethylene Glycol Dimethacrylate; D011092:Polyethylene Glycols; D002482:Cellulose