PREPARATION AND CHARACTERIZATION OF THERMOSENSITIVE MUCOADHESIVE IN_SITU GELS FOR NASAL DELIVERY OF ONDANSETRON HYDROCHLORIDE

Abstract

A nasal mucoadhesive thermo reversible in-situ gel appears very attractive since it is fluid-like prior to nasal administration and can thus easily be installed as a drop allowing accurate drug dosing. The feasibility of developing an efficacious intranasal formulation of the potent antiemetic drug Ondansetron HCL has been undertaken in this work. The ultimate goal is to circumvent the first-pass elimination of the drug when taken orally. Poloxamers P407 and P188 (20/5% w/v) were used using cold method to prepare thermo reversible gels as they have excellent thermo-sensitive gelling properties, water solubility , good drug release, low toxicity and irritation. Mucoadhesive polymers like chitosan high molecular weight (HMW), sodium carboxymethyl cellulose low molecular weight (LMW) and polyvinylpyrrolidone K30 (PVP) were used at concentration of 0.5 % (w/v) to form thermo reversible gels. Three nasal in-situ gels with desirable T sol-gel in the range of 30-35ºC were developed. pH, mucoadhesion, rheological measurements, in vitro release and ex-vivo permeation studies were performed to evaluate the prepared gels. The incorporation of chitosan to poloxamer polymers showed significant increase in the mucoadhesion ability. The prepared gels exhibited non-Newtonian shear thinning behavior at 35ºC. Drug contents were in the range of 97.8-100.1%. The release pattern was enhanced by the PVP polymer, in opposition; chitosan and NaCMC retarded it. Concerning permeation through sheep nasal mucosa, the steady state flux (J ss) of the three formulae was found to be 3.57, 5.64 and 3.81 µg/cm 2 .min., respectively. No marked alteration in the histological structure of the nose epithelial cell membrane of male Wister rats after application of the formed gels was observed to confirm their safety. The bioavailability for the optimized formulation was 86.98% providing that intranasal route could be promising for Ondansetron HCL delivery. INTRODUCTION Nasal delivery is increasingly considered to be an alternative route for drugs that currently require parentral administration. As a site for systemic absorption the nasal route provide means of avoiding first pass metabolism (Ultarwar et al., 2012). The development of in situ gel systems has received considerable attention over the past few years. These systems possess potential advantages like simple manufacturing process, reduced frequency, ease of administration, improved patient compliance and comfort (Miyazaki et al 2003). In-situ gel forming drug delivery is a type of mucoadhesive drug delivery system. In contrast to very strong gels, they can be easily applied in liquid form to the site of drug absorption, swell to form a strong gel capable of prolonging the residence time of the active substance. Both natural and