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 ANUTA1*
1 University of Medicine and Pharmacy „Carol Davila”, Faculty of
Pharmacy, 6th Traian Vuia street, 020956, Bucharest, Romania
2 University of Medicine and Pharmacy Targu Mures, 38th Gh.
Marinescu street, 540000, Târgu Mureș, Mureș, Romania
*corresponding author: vali_anuta@yahoo.com
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Abstract:

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.

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