Yingqing Ran
Genentech, Inc. USA
Title: Systemic in vitro and in vivo evaluation of the feasibility of Amorphous solid dispersion for a B-RAF (Rapidly Accelerated Fibrosarcoma) inhibitor
Biography
Biography: Yingqing Ran
Abstract
It is well acknowledged that oral bioavailability of a drug candidate is often influenced by factors such as the permeability, physico-chemical properties, and metabolism of the drug. Among the physico-chemical properties, solubility and dissolution rate are considered critical factors affecting the oral bioavailability. For compound G-F, a potent and selective B-Raf inhibitor with poor solubility and solubility limited absorption at high doses, we evaluated a spray-dried amorphous dispersion (SDD) formulation to improve the solubility. A combination of theoretical solubility prediction and in vitro dissolution were used to predict the in vivo exposure of G-F. The predicted value was found to have good agreement with the in vivo exposure resulted from adminstering the crystalline and amorphous form of G-F to rats. In general, this combined approach demonstrated that the amorphous form of G-F offers an advantage over the crystalline form of G-F in terms of solubility; in vitro dissolution and in vivo absorption that were predictable and were consistent with literature. This systemic approach provides a great value for compound development.