Contributions on formulation and preliminary evaluation of ocular colloidal systems of chitosan and poloxamer 407 with bupivacaine hydrochloride

Abstract

The aim of this paper was the formulation and preliminary evaluation of colloidal systems with improved mechanical and mucoadhesive properties in order to increase ocular retention time and drug bioavailability. Polymeric mixtures of chitosan (0.3%), a pH-sensitive polymer, and poloxamer 407 (12%, 15%, 18%), thermoresponsive polymer, with bupivacaine hydrochloride (0.25%) were prepared. Gelling temperature, wettability, rheological behaviour and in vitro drug release were evaluated. The formulation containing 15% poloxamer 407 is converted to a colloidal dispersion at 35°C, the temperature of the ocular surface. Contact angle values of colloidal systems at physiological temperature (35°C) were lower than those corresponding to formulations at non-physiological temperature (25°C), indicating a higher spreadability over the ocular surface. Rheological studies have shown pseudoplastic behaviour and the poloxamer concentration increased the viscosity of the formulations. In vitro bupivacaine hydrochloride delivery from colloidal systems revealed that drug release mechanism followed Higuchi model. The colloidal dispersions with chitosan and poloxamer 407 could be viable alternatives to increase the bioavailability of bupivacaine hydrochloride in topical ocular anaesthesia.