Polymeric matrix of hydroxypropylmethylcellulose and xanthan gum for controlled delivery of diltiazem hydrochloride in rabbits

Abstract

Effects of matrices consisting of htdroxypropylmethylcellulose (HPMC) and xanthan gum (XG) (1:1) as well as types of filler were studied for controller release of diltiazem hydrochloride, a water soluble drug. Results indicated that drug released from matrices with only HPMC was faster than those with mixed polymers. When amount of polymer was increased, the trend of decreasing drug release was observed. Drug release from matrices incorporated with soluble filler, lactose was greater than those composed of insoluble filler, dibasic calcium phosphate. In vitro dissolution testing in various media demonstrated that the formulations which were similar to Cardill® (120 mg diltiazem hydrochloride tablet) were those with 7% HPMC and GX in dibasic calcium phosphate (DBCP), 10% HPMC and XG in DBCP and lactose (2:1) and 15% HPMC and XG in lactose. All formulations were studied in rabbits. It was found that there were statistically significant differences among the area under the plasma drug concentration-time curves as well as the peak plasma drug concentrations of all formulations (p˂0.05). Individual test formulation was bioinequivalent to the reference product (Cardill®) with respect to both the extent and the rate of drug absorption into systemic circulation. The formulation with 10% HPMC and XG in DBCP and lactose (2:1) appeared to be as closely bioavailable as Cardil®. The time to peak plasma concentration of all formulations ranged from 3.10-4.50 hr. The elimination half-life was between 1.17-1.74 hr.