Precipitation of poorly soluble drugs

In vivo drug precipitation has been a major issue facing poorly soluble drugs, especially weak bases. This work aims to provide a framework on how to use the Artificial Stomach Duodenum (ASD) System to assess the extent of precipitation of poorly soluble compounds under biorelevant conditions.

The concentration profiles measured in the ASD System are used as inputs in the gCOAS^® ASD model to estimate the nucleation and growth kinetic parameters. These crystallization kinetic parameters are then used in the gCOAS GI tract model to simulate in vivo precipitation under human fasted conditions and to calculate the fraction absorbed as a function of dose.

Topics covered

In this webinar you will learn about how…

• Precipitation experiments of a poorly soluble free base were performed in the ASD setup under dog fasted conditions
• A model for the ASD system was built in gCOAS and the precipitation kinetic parameters were estimated from the experimental desupersaturation curves
• An in vivo oral absorption model for the free base was developed in gCOAS and the estimated precipitated kinetic parameters were implemented to account for the impact of precipitation on the fraction absorbed for different dose strengths.

Presenter(s)

Kaoutar Abbou Oucherif, Associate Senior Consultant Engineer, Eli Lilly and Company

Kaoutar Abbou Oucherif is an Associate Senior Consultant Engineer at Eli Lilly and Company. She is a member of Eli Lilly’s modelling group and has been a part of the Systems-based Pharmaceutics Alliance since its founding. Kaoutar earned her PhD in Chemical Engineering at Purdue University.