Formulation and Optimisation of Sustained Release Spray-Dried Microspheres of Glipizide Using Natural Polysaccharide

Abstract

The objective of this study was to investigate the combined influence of three independent variables in the preparation of glipizide microspheres by the spray-drying method. A three factor, three level Box-Behnken design was used to derive polynomial equations and construct response surface plots to predict responses. The independent variables selected were concentration of polymer (xyloglucan) (X1), amount of crosslinking agent (X2), and feed rate (X3). Fifteen batches were prepared and evaluated for percentage drug entrapment and time for 80% drug release (t₈₀). Response surface plots were constructed to demonstrate the combined effects of factors X1, X2, and X3 on response percent entrapment. The optimal microsphere preparations displayed a percent entrapment between 96.96 and 98.11 and a t₈₀ between 420 and 439 min. The microspheres had particle size between 3 and 6 microns, and differential scanning chromatography thermograms showed the presence of glipizide in amorphous form in microspheres.

LAY ABSTRACT: Multiparticulate dosage forms are pharmaceutical formulations in which the active substance is present as number of small independent subunits. The microspheres as drug delivery systems are especially suitable for providing oral controlled release formulations with low risk of dose dumping, Microspheres can be blended suitably to attain different release patterns. Glipizide is recommended orally for treatment of type II diabetes and is administered in 2 or 3 doses of 2.5 to 10 mg per day. The development of controlled-release dosage form would offer effective control by releasing drug over period of time. The present work describes formulation of microspheres containing glipizide using the tamarind seed polysaccharide or xyloglucan as carrier. The spray-drying method was used to formulate the microspheres and variables (concentration of xyloglucan, amount of crosslinking agent, and feed rate) affecting performance parameters such as time for 80% drug release and percent drug entrapment were optimized using a statistical design (Box Behnken design). The microspheres had particle size between 3 and 6 microns, had entrapment between 97 and 99%, and sustained the drug release beyond 7 hours.