The present work deals with the development and characterization of lercanidipine hydrochloride pulsatile drug delivery system for chronomodulated therapy for improvement in therapeutic index and efficacy of lercanidipine HCl. The basic design consists of an insoluble hard gelatin capsule body, filled with eudragit coated chitosan microcapsules of lercanidipine HCl and sealed with a hydrogel plug. The entire device was enteric coated with cellulose acetate phthalate, so that the variability in gastric emptying time can be overcome and a colon-specific release can be achieved. The lercanidipine hydrochloride chitosan microspheres were prepared by emulsion cross linking method in four batches A, B, C, D by varying drug to polymer ratio and evaluated for the particle size, drug content and in-vitro release profile. From the obtained results; two better formulations were selected and enteric coated with Eudragit S-100 and Eudragit L-100 in the ratios of 1:2 by solvent evaporation method. These two enteric coated formulations were selected for further fabrication of pulsatile capsule. Different hydrogel polymers were used as plugs, to maintain a suitable lag period and it was found that the drug release was controlled by the proportion of polymers used. In-vitro release studies of pulsatile device revealed that, increasing the hydrophilic polymer content resulted in delayed release of lercanidipine HCl from microcapsules. The mechanism of drug release was found to be Korsmeyer-Peppas model for optimized formulations. FT-IR and DSC studies revealed the absence of any drug-excipients interaction. Stabilitystudies carried out on optimised microspheres showed that the microspheres remained stable during the stability period without any significant changes in their physico-chemical properties.
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