Preparation of the Controlled Release Chitosan Microspheres and Optimisation of the Formulation Parameters

Abstract

The efficacy of many drugs is often limited by their potential to reach the site of therapeutic action. In most cases (conventional dosage forms), only a small amount of administered dose reaches the target site, while the majority of the drug distributes throughout the rest of the body in accordance with its physicochemical and biochemical properties. In recent years, controlled drug delivery formulations and the polymers used in these systems have become much more sophisticated, with the ability to do more than simply extend the effective release period for a particular drug. In the present study, an attempt has been made to prepare microspheres by ionotropic gelation method using chitosan as a polymer and sodium tripolyphosphate (TPP) as a cross linking agent. Chitosan is a biodegradable natural polymer with a great potential for pharmaceutical applications due to its good biocompatibility, nontoxicity and mucoadhesion. TPP is an extensively researched well established, charged, non toxic, multivalent, anionic crosslinking agent with five bonding sites on the molecules. Metformin hydrochloride loaded chitosan - TPP microspheres were prepared by dropping the drug containing solution of chitosan into TPP solution. The droplets instantaneously formed gelled spheres by the ionotropic gelation. The influence of drug concentration, drug-chitosan concentration, and pH of TPP solution was studied. The microspheres were characterized by their percentage yield, particle size, surface morphology, encapsulated amount of drug and in vitro drug release rate. Release studies were done in buffer (pH 1.2) and subsequently in buffer (pH 6.8). The release of drug from microspheres was greatly affected by pH of TPP solution, chitosan concentration, and drug concentration. After studying various parameters it was examined that highest encapsulation efficiency and highest percentage release was achieved at pH 9 having TPP conc. 2% (w/v), chitosan conc. 1% (w/v) and drug conc. of 1.5% (w/v). Morphology and stability of microspheres was observed to be good as compared to others at these optimized values. Chitosan microspheres cross-linked by a combination of tripolyphosphate, not only had a good shape, but also had good pH-responsive drug release properties. High drug incorporation in chitosan – TPP microspheres could be achieved by ionotropic gelation method without using any toxic chemicals which causes undesirable effects. Hence this method is of particular interest in the pharmaceutical field. Also the ionotropic gelation can be carried out under very mild conditions using simple equipments. The control of various manufacturing parameters plays a very important role in obtaining microspheres of good sphericity, high yield and high drug encapsulation.