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

• DOI: 10.1021/acs.cgd.5b01341
• Publication Date: 2016-01-04T21:53:13Z
• Authors: Luis Almeida e Sousa; Susan M. Reutzel-...; Gregory A. Stephe...; Lynne S. Taylor
• Keywords: Supersaturation

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 the kinetics of dissolution, there is relatively little comparison different degrees supersaturation achieved by using state forms same compound. Recent studies from our group demonstrated that maximum achievable dictated form drug. Liquid–liquid phase separation (LLPS) occurs at concentrations above this value. Herein, it was hypothesized upper limit can be dissolution various high solids also governed solubility. To test hypothesis, behavior a model compound, CRH1, were investigated variety techniques. With exception CRH1 crystalline free base, all generated solutions. The extent supersaturation, onset crystallization time, area under curve increased significantly when polymer with inhibitory properties present in medium incorporated formulation (in case dispersions). In presence polymeric inhibitor, several forms, including dispersion dissolved underwent LLPS, generating drug-rich phase. Other prior attaining showed no evidence LLPS (co-crystal glass forms). These should aid selection help understand how achieve maximized vivo.