Preparation and in vitro in vivo characterization of polyelectrolyte alginate–chitosan complex based microspheres loaded with verapamil hydrochloride for improved oral drug delivery

摘要

Verapamil hydrochloride (VH) is a calcium channel blocker. It shows short biological half life (t1/2 4 h) and hence high dosage frequency is required to maintain the desired plasma level upon its oral administration to cardiac patients. Therefore, the present study aims to prepare the controlled release formulation of VH loaded in the alginate–chitosan complex based microspheres. It also involves the study of the effect of drug to polymer ratio and the effect of different concentrations of crosslinking agent (CLA). Chitosan-alginate microspheres were prepared with two different drug to polymer ratios and two different concentrations of CLA (sodium tripolyphosphate) by solvent extrusion method; and were characterized for drug content, particle size, compressibility index, swelling index, surface morphology, in vitro floatability, FTIR, XRPD, DSC, in vitro drug release study and in vivo study. The characterization of fabricated microspheres showed spherical particles with smooth surface of particle size ranging from 1,123.50 to 1,534.40 µm, high drug content (74.8–84.4 %), good flow properties indicated by compressibility index (3.38–7.18 %), high percent swelling index, good floatability (55.4–84.6 % after 12 h). FTIR, XRPD and DSC data supported the formation of a polyelectrolyte alginate chitosan complex as a controlled release microparticulate drug delivery system for verapamil. Microspheres showed 85.0–95.45 % in vitro drug release in 12 h. The prepared microspheres showed controlled drug release during in vivo study with almost same Cmax as that of pure drug but with greater AUC. It was concluded that the alginate–chitosan polyelectrolyte complex based microspheres could be considered for controlled drug delivery of verapamil hydrochloride. The microspheres prepared with high drug to polymer ratio showed good drug content, compressibility index, swelling index, surface morphology, floatability, greater in-vitro drug release and in vivo bioavailability. An increase in concentration in CLA showed a decrease in the compressibility; increase in swelling in pH 1.2, pH 6.8 buffer media; and increase in drug release.