DESIGN AND DEVELOPMENT OF PULSIN-CAP CHRONOMODULATED DRUG DELIVERY OF SELECTIVE ANTI-ANGINAL DRUG: AN IN VITRO AND IN VIVO EVALUATION

Abstract

Objective: In the current work, an attempt was made to formulate the chrono pharmaceutical drug delivery of Ivabradine HCl to the colon. A time-delayed capsule was prepared by sealing the micro particles inside a gelatin capsule made up of erodible hydrogel plug. Methods: The microparticles were formulated by counter-ion elicited aggregation methodology. A natural polymer such as chitosan was chosen as polycation and smaller molecular electrolytes like sodium citrate, sodium sulphate and sodium tripolyphosphate were chosen as poly-anions. The formulated aggregate microparticles were tested for surface morphology, size distribution, in vitro un-harness and drug excipient interaction. Optimized microparticles formulations were carefully chosen on the basis on dissolution studies. The whole device was enteric coated and hydrogel plug was placed in the capsule opening. Results: The pulsatile capsule was found to be acceptable to delay the drug release in small intestinal fluid and eject out the plugin colonic fluid, thus releasing the microparticles into colonic fluid after a lag time criterion of 5 h. To mimic the pH changes along the GI tract, three dissolution media with pH 1.2, 6.8 and 7.4 were sequentially used. FT-IR study established that there was no interaction between the drug and polymer. Among all the formulations, Ivabradine HCl prepared with sodium tripolyphosphate showed prolonged release for a period of 12 h. Conclusion: The obtained results revealed the system's capability to defer the drug release for a programmable period and prevent a sharp increase in blood pressure during the early morning hours when the risk of heart attack is the greatest.