E. Nicolaides et al., Forecasting the in vivo performance of four low solubility drugs from their in vitro dissolution data, PHARM RES, 16(12), 1999, pp. 1876-1882
Purpose. To assess the usefulness of biorelevant dissolution tests in predi
cting food and formulation effects on the absorption of four poorly soluble
, lipophilic drugs.
Methods. Dissolution was studied with USP Apparatus II in water, milk, SIFs
p, FaSSIF, and FeSSIF. The in vitro dissolution data were compared on a ran
k order basis with existing in civet data for the tested products under fas
ted and fed state conditions.
Results. All drugs/formulations showed more complete dissolution in bile sa
lt/lecithin containing media and in milk than in water and SIFsp, (USP 23).
Comparisons of the in vitro dissolution data in biorelevant media with in
vivo data showed that in all cases it was possible to forecast food effects
and differences in absorption between products of the same drug with the p
hysiologically relevant media (FaSSIF, FeSSIF and milk). Differences betwee
n products (both in vitro or in vivo) were less pronounced than differences
due to media composition (in vitro) or dosing conditions (in vivo).
Conclusions. Although biorelevant dissolution tests still have issues which
will require further refinement, they offer a promising in vitro tool for
forecasting the in vivo performance of poorly soluble drugs.