Novel interpenetrated polymer network microbeads of natural polysaccharides for modified release of water soluble drug: in-vitro and in-vivo evaluation

Abstract

The objective of this work was to prepare novel interpenetrating polymer network (IPN) microbeads of tamarind seed polysaccharide and sodium alginate for controlled release of the water soluble drug, diltiazem hydrochloride. The diltiazem-Indion 254(®) (a cation exchange resin) complex was prepared and the resulting complex was entrapped within IPN microbeads prepared by ionotropic gelation and covalent crosslinking. Microbeads were characterized by scanning electron microscopy, differential scanning calorimetry, thermogravimetric analysis, X-ray diffraction and Fourier transform infrared spectroscopy (FTIR) analyses, and evaluated for swelling, in-vitro release and preclinical pharmacokinetics. The unformulated drug showed complete dissolution within 60min, while drug release from diltiazem-ion-exchange resin complex was extended for 2.5h but IPN microbeads extended the release for longer period. The ionically crosslinked microbeads released the drug for 6h, while dual crosslinked microbeads extended the release for 9h. The microbeads containing a higher amount of glutaraldehyde released the drug very slowly. The results of in-vivo pharmacokinetics of pure drug and drug-loaded IPN microbeads showed that the microbeads demonstrated prolonged release supporting the findings of in-vitro studies. Prepared IPN microbeads showed prolonged in-vitro and in-vivo release for diltiazem, indicating that this IPN would be a versatile delivery system for water soluble drugs.