Experimental Methods to Study Interplay of Dissolution, Solubility and Permeability in Formulation Development

Balint Sinko, Pion Inc, Billerica, USA

Development strategy for insoluble compounds requires not only measurements of the solubility enhancement from formulations but also the assessment for the effect formulations having on permeability. An introduced dissolution-permeability (µFLUX) measurement platform allows simultaneous monitoring for both effects enabling in vitro setup for early in vivo predictive formulations testing.

Ability to measure concentration of free (solubilized) drug in situ is critical necessity in formulation research because any off-line solution handling can disturb quasi-stable (kinetic) phase that low soluble compounds often form in the presence of excipients. Case studies involving two different detection techniques based on fiber-optic UV measurements and potentiometric free drug sensors (FDS) will be presented. These case studies will highlight:

 

·    Combining dissolution and permeability assays for better formulation design, understanding the food effect on bioavailability and more realistic IVIVC;

·    Studying if solubility enhancement in the bio-relevant media leads to the same gain in the absorption and bioavailability;

·    Real time concentration monitoring of free drug in the presence of lipid passed formulations, nanoparticles and binding proteins;

·    Monitoring in real time the free API fraction released from nanoparticles and predicting absorption enhancement from nanoparticle formulations;

·    Developing of predictive in vitro method to monitor powder/formulation dissolution and concomitant precipitation processes in dynamically changing biorelevant media;