| The unique anatomic and physiologic characteristics within the different regions of the gastrointestinal tract make it difficult to obtain drug action for more than 8 to 12 hours with conventional controlled release systems which generally follow a zero-order, first-order, or {dollar}surd{dollar}t release profile.; In this study, a new compression-coated, peroral, controlled release, self-destructing system, the hydrogel piston pump, was developed based on biopharmaceutic and pharmacokinetic principles. The objective was to provide a physiologically oriented drug release profile that changes to compensate for the decreasing rate and extent of drug absorption, with gastrointestinal transit, thereby providing action for upto 24 hours. The system consists of a core of drug and a hydrogel enclosed in a compression-coated shell of ethylcellulose. The shell contains a coated disintegrant and a delivery orifice. The release profile consists of an initial phase to compensate for the lag time, a constant zero-order release phase and a final increasing drug release phase. Each phase may be tailored for the specific drug.; The model drug used was promethazine. The absorption of promethazine was studied from the different gastrointestinal segments, in rat, and was found to be maximum from the jejunum. Based on the pharmacokinetic parameters of promethazine a dose of 55 mg was calculated with an additional 10 mg in the initial phase.; Disks were prepared using various hydrogels by both solvent casting and direct compression and their performance was evaluated. Microcrystalline cellulose was selected as the disintegrant and was granulated-coated with a mixture of Eudragit L100 and S100 to provide disintegration at a target pH of 6.5.; The final optimized system comprising of a 7 mm diameter drug core, 1 mm thick hydrogel disk containing 5% hydroxypropyl methylcellulose, 375 mg shell containing 25% of coated disintegrant, 356 {dollar}mu{dollar}m delivery orifice and an immediate release layer was evaluated in vivo, in human subjects.; The in vivo study indicated that the developed system was successful in achieving prolonged systemic levels of the drug. The mean strength of retardation of 3.13 indicates a strong retardation over the immediate release formulation. The objective of the study was therefore achieved. |
