Abstract

DEVELOPMENT OF CONTROLLED RELEASE FORMULATION OF AN ANTIEMETIC DRUG USING NOVEL PARENTERAL DRUG DELIVERY SYSTEMS

Mirajkar Reshma*, Madgulkar Ashwini and Kulkarni Shirish

Abstract

The overall aim of this work was to develop Controlled release parenteral drug delivery system using in situ gel forming mechanism for an anti-emetic drug typically co-administered with chemotherapeutic agents. The study involved formulation of the drug Ondansetron Hydrochloride in an in situ gel forming system involving thermoreversible polymer Pluronic F127 (PF127), copolymer Hydroxypropylmethyl cellulose (HPMC) K100M and temperature modifier Polyethylene glycol 400 (PEG 400) to form an optimized solution intended to be administered subcutaneously. Ondansetron Hydrochloride is parenteraly administered twice a day in chemotherapy induced nausea and vomiting over a period of 5 days. The formulation was optimised and evaluated for all prerequisites of parenterals and other parameters like gel formation at 37°c, viscosity, rheology, gel stability, gel strength, invitro drug release, in vivo pharmacokinetics and stability studies. The formulation showed rapid in situ gelation at 37°c forming stable and viscous gel showing thixotropic behavior, following all prerequisites of a parenteral product. The in vitro drug release was found to be over 95% in Simulated Body fluid pH 7.4 at 37°C over a prolong period of 5days and the invivo pharmacokinetic evaluation showed increase in tmax, Cmax and AUC as compared to immediate release formulation which may be attributed to the slow diffusion of the drug from the polymeric matrix. The formation invivo of a stiffer gel confirmed the in situ gelation of the formulation and it was found to be biocompatibile by the histopathological studies. The formulation was physically and chemically stable at ambient temperature, accelerated conditions and at refrigerator conditions with most suitable storage condition at the refrigerator temperature.

Keywords: anti-emetic, Pluronic F127, in situ gelling system, thermosensitive.