Selection of the most suitable dissolution method for an extended release formulation based on IVIVC level A obtained on cynomolgus monkey.
OBJECTIVE
The purpose of this study is primarily to identify the most suitable in vitro dissolution method(s) for their ability to predict the in vivo performance of extended release prototype tablet formulations designed for a new chemical entity, Biopharmaceutic Classification System class II drug, weak base, based on the data collected in cynomolgus monkey.


METHODS
Different types of buffer at different pH were selected as dissolution medium resulting in a broad variety of release patterns (slow to fast). The in vivo and in vitro data were put in relation.


RESULTS
As a consequence of the discrimination between both tested formulations, the in vitro-in vivo correlation (IVIVC) qualities and shapes changed significantly. The obtained level A showed that the simple HCl medium was superior to biorelevant media and media containing surfactant when investigating IVIVCs in cynomolgus monkey. In addition, the results of dissolution in HCl suggested rather a diffusion mechanism of the extended release matrix formulation as the main factor of the release.


CONCLUSIONS
Adjusting dissolution testing conditions to match the behavior of the formulations in vitro with that in vivo by taking into account the properties of the drug and the formulation is a straightforward and useful approach in identifying a predictive method in the development of the IVIVC. These investigations will definitely help by derisking of new formulations as well as by rating changes in existing formulations with regard to their impact on bioavailability before entry into human.
Scheubel
Emmanuel
E
Galenical and Analytical Development, F. Hoffman-La Roche Ltd., Pharmaceutical Division, Basel, Switzerland. emmanuel.scheubel@roche.com
Adamy
Laurent
L
Hoffart
Valerie
V
Cardot
Jean Michel
JM
D000818:Animals; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003692:Delayed-Action Preparations; D006863:Hydrogen-Ion Concentration; D008252:Macaca fascicularis; D023421:Models, Animal; D008954:Models, Biological; D004364:Pharmaceutical Preparations / Q000737:chemistry* / Q000378:metabolism; D010865:Pilot Projects; D012995:Solubility; D012997:Solvents / Q000737:chemistry*; D013501:Surface-Active Agents / Q000737:chemistry; D013607:Tablets
D003692:Delayed-Action Preparations; D004364:Pharmaceutical Preparations; D012997:Solvents; D013501:Surface-Active Agents; D013607:Tablets