Development of Chronopharmaceutical Drug Delivery System for the Treatment of Angina Pectoris

Abstract

The present study was aimed at exploring the feasibility of time and pH dependent colon specific, pulsatile drug delivery of anti-anginal drugs as dual release dosage form to modulate the drug level in synchrony with the circadian rhythm of Angina Pectoris. Hence, an attempt was made to develop a novel dosage form (Pulsincap) by using a Chronopharmaceutical approach for better management of Angina with combination therapy. From the results of above executed experiments, it can be summarised as, Preformulation studies such as organoleptic characteristics, melting point, solubility, hygroscopicity, UV analysis of Trimetazidine hydrochloride and Metoprolol succinate were found to comply with official standards. DSC analysis data confirmed that the drugs were pure and they still present in their lattice structure in the physical mixture with polymers and excipients. They exhibited a sharp endothermic peak at their corresponding melting points. About nine different formulations of TMH microspheres were prepared by W/O/O double emulsion solvent evaporation method using eudragit polymers by varying polymer concentration and stirring rate. Micromeritic properties of TMH microspheres were found to be satisfactory. Results revealed that the prepared microspheres had excellent flow property. SEM results indicated that formulation prepared at moderate stirring rate and drug-polymer ratio of 1:2 showed a symmetrical smooth surfaced microspheres. Thus, in this present research work, it was proved that novel Pulsincap technology could be most ideal to modulate the drug level in synchrony with the circadian rhythm of Angina pectoris. Also, it was concluded that an innovate approach of managing Anginal symptoms with combination of haemodynamic agent and cytoprotective anti-ischemic agent was no longer available commercially and it could be recommended for effective treatment. The developed Pulsincap dosage form is far superior to the available conventional dosage forms of Trimetazidine hydrochloride and Metoprolol succinate.