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RESEARCH CONCERNING THE DEVELOPMENT OF A BIORELEVANT DISSOLUTION TEST FOR FORMULATIONS CONTAINING NORFLOXACIN. I. MODELLING OF IN VITRO RELEASE KINETICS

IULIA ANTOANETA PREDA¹, ION MIRCIOIU², CONSTANTIN MIRCIOIU¹, GEORGE CORLAN¹, GABRIELA PAHOMI¹, IRINA PRASACU¹, VALENTINA ANUTA^1*

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The paper presents a study of norfloxacin release kinetics from solid oral formulations in compendial and biorelevant media simulating the composition of the gastric and intestinal contents before and after meal intake in terms of establishing the predictive kinetic models to be further correlated with in vivo pharmacokinetic profiles. Norfloxacin release kinetics was strongly dependent on the dissolution medium as well as on formulation. Results indicated a very rapid and complete dissolution in compendial simulated gastric fluid (SGF) and in acetate buffer (pH 4.0), while in biorelevant media the release followed a different release kinetics, probably connected with the variability of solubility of norfloxacin in the proximity of the isoelectric point. Though bile salts were expected to increase the solubility of norfloxacin by the intermediate of micelles, this result appeared to be significant only under fed state simulated conditions (100% release versus 32% under fasting conditions). Experimental data was fitted using Higuchi, Peppas, Noyes- Whiney and Weibull models, in order to establish the most relevant predictive kinetic models. All analysis suggested a two phase evolution of the release phenomena. This change in behaviour was thought as a consequence of both norfloxacin solubility changes during the release and its including in micelles by means of bile salts and lecithin.