Abstract

Background
Food may affect the oral absorption of drugs. Purpose: The aim of the present study was to investigate the influence of food on the oral absorption of Clarithromycin by evaluating the effect of media parameters such as; pH, bile secretions and food composition on the release of the drug from immediate release tablet, using in vitro and in silico assessments.

Method
The solubility, disintegration and dissolution profiles of Clarithromycin 500 mg immediate release tablets in compendial media with/without the addition of homogenized FDA meal as well as in biorelevant simulated intestinal media mimicking fasting and fed Conditions were determined. These in vitro data were input to GastroPlusTM, which was used for developing a physiological absorption model capable of anticipating the effect of food on Clarithromycin Absorption. Level A in vitro – in vivo linear correlations were established using mechanistic absorption modeling based deconvolution approach.

Results
Media pH has a profound effect on clarithromycin solubility, tablet disintegration and drug release. Clarithromycin has lower solubility in the biorelevant media compared to other media, due to complex formation with bile salts. Clarithromycin tablets exhibited prolonged disintegration times and reduced dissolution rates in the presence of the standard FDA. The simulation model predicted no significant food effect on the oral bioavailability of Clarithromycin. The developed IVIVC model considered SIF, acetate buffer and FaSSIF media to be the most relevant from the Physiological standpoint.

Conclusion
the intake of standard FDA meal may have no significant effect on oral bioavailability of Clarithromycin immediate release tablet