Abstract

PRECLINICAL PHARMACOKINETIC EVALUATION OF STARCH ACETATE AND CHITOSAN MICROPARTICLES OF GLIPIZIDE

P. Veera Lakshmi, K.P.R Chowdary*, A. Prameela Rani and S.V.U.M. Prasad

Abstract

Recently much emphasis is being laid on the development of microparticles because of their potential benefits such as increased bioavailability, reduced risk of systemic toxicity, reduced risk of local irritation and predictable gastric emptying. The preparation and in vitro (drug release) evaluation of microparticles of glipizide using i) starch acetate, a new modified starch and ii) chitosan, a new mucoadhesive polymer are reported earlier. The microparticles prepared using both the polymers exhibited good in vitro controlled release of glipizide over 12 h. The objective of the present study is preclinical pharmacokinetic evaluation of selected glipizide microparticles (SAF2 and CHF3) in comparison to glipizide pure drug in healthy rabbits (n=6). The products were tested orally at a dose equivalent to 0.4 mg/kg of glipizide. Plasma glipizide concentrations were determined by a reported and revalidated HPLC method. The biological half life (t1/2) of glipizide pure drug estimated (3.45 h) was in good agreement with the literature value of 2-5 h. The t1/2 of glipizide was slightly elongated with microparticles. The absorption of Glipizide was very rapid when administered as pure drug and was slow from both the microparticles tested. Based on (AUC)o α , the relative bioavailability (BA) of glipizide from microparticles SAF2 and CHF3 was 105.41 % and 113.95% respectively when compared to glipizide pure drug (100%). A good level A correlation was observed between percent drug released (in vitro) and (AUC)o α (in vivo) with both the microparticles. Thus, the results of preclinical pharmacokinetic studies indicated that glipizide was absorbed slowly from microparticles and the plasma drug concentrations were sustained over longer period of time when compared to glipizide pure drug.

Keywords: Glipizide, Microparticles, Chitosan, Starch acetate, Preclinical evaluation, Pharmacokinetics.