Abstract

CALCIUM SILICATE BASED MICROSPHERES OF THEOPHYLLINE FOR GASTRO RETENTIVE FLOATING DRUG DELIVERY: PREPARATION, IN VITRO CHARACTERIZATION AND IN VIVO INVESTIGATIONS

Kedar Prasad Meena* and J. S. Dangi

ABSTRACT

Gastroretentive dosage forms have potential for use as controlled-release drug delivery systems. Multiple unit systems avoid the all-or-none gastric emptying nature of single-unit systems. Theophylline, a fast and short-acting meglitinide analog used for long term treatment of asthma was chosen as the drug candidate since it is indicated for the development of a dosage form with increased GRT. It has a very short half-life (2-4 h), low bioavailability (49%) and poor absorption in the upper intestinal tract. So a controlled release system designed to increase its residence time in the stomach without contact with the mucosa was achieved through the preparation of floating microspheres by the emulsion solvent diffusion technique consisting of calcium silicate (CaSi) as porous carrier; theophylline (TH), as an antiasthamatic agent; and Eudragit S-100 as polymer. The prepared formulations were characterized for micromeritic property, in vitro floating behavior, and drug loading, and surface morphology, Interaction study by FTIR, DSC and XRD followed by pharmacokinetic study. The microspheres were found to be spherical in shape and porous. The release rate was determined in simulated gastrointestinal fluids at 37±1˚C. The formulation demonstrated favorable in vitro floating and release characteristics. The drug encapsulation efficiency was 88±1.2. The pharmacokinetic study of developed formulation compared with multi dose marketed formulation and reveals maintenance of plasma drug concentration, which is comparable that of marketed formulation. The designed system, combining excellent buoyant ability and suitable drug release pattern, could possibly be advantageous in terms of increased bioavailability of theophylline.

Keywords: Emulsion solvent diffusion, Calcium silicate, Microspheres, Theophylline.