Formulation and Characterization of Mucoadhesive Microspheres Using Verapamil Hydrochloride as Model Drug

The objective of the current investigation is to reduce dosing frequency and improve patient compliance by designing and systematically evaluating sustained release microspheres of verapamil. Frequent administration and variable low bioavailability (40-60%) after oral administration are problems of conventional dosage forms of verapamil can be attenuated by designing it in the form of mucoadhesive microspheres which would prolong the residence time at the absorption site to facilitate intimate contact with the absorption surface and thereby improve and enhance the bioavailability. Verapamil-loaded mucoadhesive microspheres were successfully prepared by emulsification-internal gelation technique with a maximum incorporation efficiency of 93.29±0.26%. The scanning electron microscopic study indicated that the microspheres were spherical in shape and the drug remained dispersed in the polymer matrix at amorphous state, which was further confirmed by x-ray diffraction analysis. The in vitro wash-off test indicated that the microspheres had good mucoadhesive properties. The wash-off was faster at simulated intestinal fluid (phosphate buffer, pH 7.4) than that at simulated gastric fluid (0.1 M HCl, pH 1.2). The in vitro drug release mechanism was non-fickian type controlled by swelling and relaxation of polymer. There was no significant change in drug content and cumulative drug release of drug-loaded microspheres stored at different storage condition after 8 weeks of study. INTRODUCTION: Verapamil hydrochloride, a calcium channel blocker, is widely used for the treatment of angina pectoris, hypertension and arrhythmias. It is administered orally (tablets, capsules, sustained release tablets/capsules) and parenterally (intravenous). The usual dose of verapamil is 200-280 mg/day. The conventional tablet and capsule is administered 3 or 4 times a day due to its short biological half-life of about 2-5 hr. The problems of frequent administration and variable low bioavailability (40-60%) after oral administration of conventional tablet or capsules have been attenuated by designing verapamil in the form of sustained release tablet or capsules. The sustained release forms are administered two to four times a day due to its limited residence time in the gastrointestinal tract. The mucoadhesive microcapsules of verapamil would prolong the residence time at the absorption site to facilitate intimate contact with the absorption surface and thereby improve and enhance the bioavailability. The previous studies reported the mucoadhesive drug delivery systems of verapamil in the form of tablets for oral route and transdermal patches; however, there is no report on mucoadhesive microcapsules.