Supersaturation Potential of Salt, Co-Crystal, and Amorphous Forms of a Model Weak Base

Abstract

High energy solids, such as salts, co-crystals, or amorphous solid dispersions, have been widely used to generate supersaturated aqueous solutions and improve drug bioavailability. However, most research on solubility enhancing strategies has focused on the kinetics of dissolution, and there is relatively little comparison of the different degrees of supersaturation achieved by using different solid state forms of the same compound. Recent studies from our group have demonstrated that the maximum achievable supersaturation is dictated by the aqueous solubility of the amorphous form of the drug. Liquid–liquid phase separation (LLPS) occurs at concentrations above this value. Herein, it was hypothesized that the upper limit of supersaturation that can be achieved from dissolution of various high energy solids is also governed by the amorphous solubility. To test this hypothesis, the dissolution and supersaturation behavior of different solid forms of a model compound, CRH1, were investigated using a variety...