Formulation and In vitro/In vivo Evaluation of Sustained Release Diltiazem Matrix Tablets

Purpose: To develop and optimise sustained release (SR) matrix tablets of diltiazem hydrochloride (DHL). Methods: DHL tablets were prepared by direct compression and consisted of hydroxyprpoylmethyl cellulose, Kollidon SR and Eudragit RSPO. A 3^2 full factorial design was applied to study the effect of polymers used on drug release from the DHL. The tablets were also evaluated for physicochemical characteristics and release kinetics. In vivo human volunteer studies were carried out on the optimised formulation with a commercial sustained release product serving as reference. Results: The physicochemical characteristics of all prepared tablets were satisfactory. The developed drug delivery system provided prolonged drug release rates over a period of 24 hours. The release profile of the developed formulation was described by the Higuchi model. Mean time of occurrence for maximum (peak) drug concentration (Tmax) was 2.05 ± 0.52 and 2.30 ± 0.57 h for the optimized and commercial formulations, respectively, while mean maximum concentration of drug (Cmax) was 501.74 ± 0.05 and 509.65 ± 0.06, ng/ml respectively. Good correlation between the dissolution profiles and bioavailability was observed using the method of linear regression analysis and correlation coefficient. Conclusion: A fair correlation between in vitro dissolution and in vivo data was found. The results obtained indicate successful development of a sustained release formulation of diltiazem.