Prediction of In Vitro Drug Dissolution into Fed-state Biorelevant Media: Contributions of Solubility Enhancement and Relatively Low Colloid Diffusivity

A model was previously derived to predict in vitro dissolution of drug into surfactant solution and showed good predictability for pharmaceutical surfactants, where surfactant-mediated enhanced drug dissolution was several fold less than enhanced solubility (about 3-fold or less) due to drug-loaded micelles exhibiting slower diffusivity than free drug. The present objective was to quantitatively assess the contributions of biorelevant mediamediated solubility and diffusivity on enhanced drug dissolution in FeSSGF and FeSSIF-V2. Three poorly water soluble drugs were subjected to dissolution into FeSSGF and FeSSIF-V2, as well as their corresponding surfactant-free media. Solubility and laser diffraction analysis of drug in FeSSGF and dynamic light-scattering studies (DLS) of drug in FeSSIF-V2 were conducted. Results showed drug-saturated FeSSGF globules and FeSSIF-V2 mixed micelles were large and slow diffusing (diffusivities of about 1 x10(-9) and 7 x10(-8) cm (2)/s, respectively), compared to free drug (about 7x10(-6) cm(2)/s) and drug-bound micelles from pharmaceutical surfactants (about 0.5-1 x10(-6) cm(2) /s). Of the three drugs, griseofulvin exhibited the greatest biorelevant media-enhanced solubility and dissolution (652-fold and 6.23-fold respectively in FeSSGF, and 190-fold and 12.7-fold respectively in FeSSIF-V2), but slow colloid diffusivity markedly attenuated large solubility benefits, particularly in FeSSGF.

Automated summary

This study quantitatively assessed the contributions of biorelevant media-mediated solubility and diffusivity on enhanced drug dissolution in FeSSGF and FeSSIF-V2. The results showed that the enhancement of solubility was attenuated by slow colloid diffusivity.