GASTRORETENTIVE FLOATING MICROSPHERE OF NATEGLINIDE: FORMULATION, EVALUATION AND EFFECT OF DRUG-POLYMER RATIO

The study aims to develop gastroretentive floating drug delivery system of nateglinide which is used in the treatment of type – II diabetes. Due to the short biological half life of drug (about 1.5 hours), frequent dosing is required to maintain its therapeutic effect. Therefore, to prolong the gastric retention of nateglinide, its oil entrapped floating microspheres (different formulations with different drug to polymer ratio) were prepared using sodium alginate by emulsion gelation method. The prepared floating microspheres were subjected to evaluation for surface characteristic, entrapment efficiency, swelling index, in vitro buoyancy and in vitro drug release. The scanning electron microscope photograph indicated that the prepared microspheres were discrete and almost spherical in shape with a hollow inner core. The entrapment efficiency was found to be in the range of 80.47 % to 91.33% for all the formulations. Drug entrapment efficiency decreased with increasing polymer concentration in floating microspheres. Average buoyancy was found to be 93 % to 98% for all the formulations. The in vitro floating test clearly showed that most of the microspheres floated for around 12 hrs. The increase in polymer concentration slightly decreased the percent yield and the drug entrapment. On the other hand the increased polymer concentration resulted into increased degree of swelling and percent buoyancy. All the formulations showed good in vitro drug release with first order release by matrix diffusion process. Overall, among the different polymer-drug ratios investigated, 1:6 drug to polymer ratio showed the best buoyancy, highest swelling index, good drug release with good entrapment efficiency. It was concluded that drug-loaded floating alginate microspheres appeared to be a suitable delivery system for nateglinide for potential therapeutic use as a hypoglycemic agent.