Biol. Pharm. Bull., 27(10),1630-1635, October 2004

Regular Articles

Classification of Loratadine Based on the Biopharmaceutics Drug Classification Concept and Possible in Vitro-in Vivo Correlation

M. Zahirul I. KHAN,* Dragica RAUL, Ruica ZANOKI, Snjeana ZIDAR, Jasna Horvat MIKULI, Lara KRIZMANI, Maja EKINJA, Boris MILDNER, and Zdravka KNEEVI

PLIVA Research Institute Ltd.; Prilaz baruna Filipovi´ca 29, 10 000 Zagreb, Croatia. * To whom correspondence should be addressed. e-mail:

Loratadine was studied both in vitro and in vivo (in healthy humans) to classify it according to the Biopharmaceutics Classification System (BCS) in order to gain more understanding of the reasons for its highly variable nature with respect to plasma time profiles, and to determine the most appropriate dissolution test conditions for in vitro assessment of the release profile of the drug from solid dose forms. Based on the solubility of loratadine determined under various pH conditions and its permeability through Caco-2 monolayers, loratadine was classified as a Class II drug. Plasma profiles were predicted by convolution analysis using dissolution profiles obtained under various pH and hydrodynamic conditions as the input function and plasma time data obtained from a syrup formulation as the weighting function. The predicted profiles based on dissolution studies done at gastric pH values were in reasonable agreement with the mean bio-data suggesting dissolution testing should be done at gastric pH values. However, the bio-data were highly variable and it is suggested this may be due, at least in part, to high individual gastric pH variability and dissolution occurring in the intestine on some occasions, and therefore, dissolution testing should also be done in simulated intestinal fluid.

Key words biopharmaceutics classification system; biorelevant dissolution testing; convolution; permeability testing; in vitro-in vivo correlation; IVIVC; loratadine