ABSTRACT

Pulsatile system is gaining a lot of interest as it increases patient compliance by means of providing time and site specific drug delivery system. The aim of the present study was to formulate and evaluate pulsatile drug delivery system of amlodipine besylate based on chronopharmaceutical approach for the treatment of hypertension. The basic design involves the preparation of cross-linked hard gelatin capsules by using formaldehyde. Due to formal-dehyde treatment the length, external diameter, thickness, weight of the capsules was increased. Then the drug diluents mixture were prepared and loaded in, which was separated by using hydrogel plugs such as HPMC 50 cP, 100 cP, K100LV, methocel K15, sodium CMC, carbopol 971 and xanthan gum at different amount. Prepared formu-lations were subjected to in vitrodrug release studies. From the in vitro dissolution studies it was found that by increasing the amount of polymer, release rate was decreased. The release rate was above 90% when we used 50 mg and 75 mg polymer (in each hydrogel plug), but in case of using 100 mg polymer the release rate was 70% to 85% in 10 h. That means, in 12 h these formulations can give a satisfactory result which is the most desire in pulsati-le drug delivery system. Furthermore, the release data of all formulations were fitted to various mathematical mo-dels such as zero order, first order, Korsmeyer Peppas, Higuchi and Hixson-Crowell kinetics. The drug release fol-lows mixed order kinetics and mechanism was found to be non-Fickian diffusion. From the result it was concluded that, all formulations showed compliance with chronotherapeutic objective of hypertension and these modified pulsincap formulations can be a best alternative for high blood pressure patient to avoid multiple dosing. However, further studies can be, performed to determine the accurate dosing and better therapeutic effect.