Chemistry Reference
In-Depth Information
Figure 7.1.
(a) A contour plot showing the fraction absorbed as functions of solubility in the
fluid of the intestinal lumen and the effective permeability as quanti
ed from the
ux in a Caco-
2 cell permeability assay. (b) A thermodynamic contribution diagram showing the sublimation
and solvation contributions to the free energy of solution.
The following two sections describe the process of TDD, both in general and as
applied to telaprevir. First, we describe the efforts undertaken at the discovery stage,
which focused on measuring and modeling absorption, optimally preparing and char-
acterizing the amorphous dispersion, and developing a suspension formulation. Next, we
discuss the translational activities that are required as the dispersion moves forward into
development. The objective here is to prepare the material for GLP preclinical
