Assessing Supersaturation and Its Impact on In Vivo Bioavailability of a Low-Solubility Compound ABT-072 With a Dual pH, Two-Phase Dissolution Method.

ABT-072 is a candidate drug evaluated for treatment of hepatitis C virus. It is an acidic compound with extremely low intrinsic aqueous solubility. An in vitro dissolution-partition system, referred as biphasic test method, was used to characterize ABT-072 prototype formulations.

Transformation pathways of cocrystal hydrates when coformer modulates water activity.

An important attribute of cocrystals is that their properties can be tailored to meet required solubility and stability specifications. But before such practical uses can be realized, a better understanding of the factors that dictate co-crystal behavior is needed. This study attempts to explain the phase behavior of anhydrous/hydrated cocrystals when the coformer modulates both water activity and co-crystal solubility.

Mechanisms by which moisture generates cocrystals.

The purpose of this study is to determine the mechanisms by which moisture can generate cocrystals when solid particles of cocrystal reactants are exposed to deliquescent conditions (when moisture sorption forms an aqueous solution). It is based on the hypothesis that cocrystallization behavior during water uptake can be derived from solution chemistry using models that describe cocrystal solubility and reaction crystallization of molecular complexes. Cocrystal systems were selected with active pharmaceutical ingredients (APIs) that form hydrates and include carbamazepine, caffeine, and theophylline.

Cocrystal formation during cogrinding and storage is mediated by amorphous phase.

Purpose: The purpose of this work was to investigate the mechanisms of cocrystal formation during cogrinding and storage of solid reactants, and to establish the effects of water by cogrinding with hydrated form of reactants and varying RH conditions during storage.

Methods: The hydrogen bonded 1:1 carbamazepine-saccharin cocrystal (CBZ-SAC) was used as a model compound. Cogrinding of solid reactants was studied under ambient and cryogenic conditions.

General principles of pharmaceutical solid polymorphism: a supramolecular perspective.

The diversity of solid-state forms that an active pharmaceutical ingredient (API) may attain relies on the repertoire of non-covalent interactions and molecular assemblies, the range of order, and the balance between entropy and enthalpy that defines the free energy landscape. It is recognized that crystallization is associated with molecular recognition events that lead to self-assembly, and that pharmaceutical function and thermodynamic stability can be altered with a slight change in the interacting molecules or their molecular network motifs. Our current understanding of pharmaceutical solids in terms of molecular recognition and complementarity provides new insights into the design and function of single and fully miscible, multiple-component solids with varying degrees of order, from amorphous to crystalline states, and in this way is leading the path to supramolecular pharmaceutics.