pH-dependent gradient release microspheres of lercanidipine hydrochloride: in vitro and in vivo evaluation

Poorly water-soluble drugs pose the problem of low availability due to their limited solubility in the varying pH of the gastrointestinal tract (GIT). The aim of the present study was to develop a pH-dependent gradient-release drug delivery system for a poorly water-soluble drug, Lercanidipine HCl, a dihydropyridine calcium channel antagonist, wherein the drug is released all along the GIT. Microspheres were prepared by quasi-emulsion solvent diffusion method. In this method solid drug was dispersed as a matrix structure using three types of pH-dependent polymers viz., Eudragit E100 (for pH 1, 2), Hydroxyl propyl methyl cellulose phthalate (for pH >= 5.5) and Eudragit S100 (for pH >= 7) in different weight ratios, pH-dependent microspheres were characterized in terms of their shape, size, production yield, drug loading and entrapment efficiency. The in vitro drug release was performed at different pH conditions. The bioavailability studies were carried out in rabbits, pH-dependent microspheres were spherical in shape and were in the size range of 288-394 mu m. X-ray diffraction studies confirmed the molecular dispersion of the drug in amorphous state. The results showed that the release rate of drug from microspheres was influenced by varying the type and concentration of pH-dependent polymers employed. The drug was released only in particular pH based on the polymer used. The in vitro release followed Fickian diffusion mechanism. The results of the bioavailability testing in rabbits suggested that the pH-dependent delivery system could improve efficiently the uptake of the poorly water-soluble drug and prolong the Tmax value in vivo. These findings suggested that a microsphere-based pH-dependent drug delivery system may be prepared for the delivery of Lercanidipine HCl for improving its bioavailability.