Perspectives in solubility measurement and interpretation

ADMET and DMPK

关键词: Solubility-pH;    shake-flask solubility;    intrinsic solubility;    thermodynamic solubility;    Henderson-Hasselbalch equation;    supersaturation;    pre-nucleation clusters, drug aggregates;    drug salts;    pharmaceutical cocrystals;   

DOI  :  10.5599/admet.686

来源: DOAJ

【 摘 要 】

Several key topics in solubility measurement and interpretation are briefly summarized and illustrated with case studies drawing on published solubility determinations as a function of pH. Featured are examples of ionizable molecules that exhibit solubility-pH curve distortion from that predicted by the traditionally used Henderson-Hasselbalch equation and possible interpretations for these distortions are provided. The scope is not exhaustive; rather it is focused on detailed descriptions of a few cases. Topics discussed are limitations of kinetic solubility, ‘brick-dust and grease-balls,’ applications of simulated and human intestinal fluids, supersaturation and the relevance of pre-nucleation clusters and sub-micellar aggregates in the formation of solids, drug-buffer/excipient complexation, hydrotropic solubilization, acid-base ‘supersolubilization,’ cocrystal route to supersaturation, as well as data quality assessment and solubility prediction. The goal is to highlight principles of solution equilibria – graphically more than mathematically – that could invite better assay design, to result in improved quality of measurements, and to impart a deeper understanding of the underlying solution chemistry in suspensions of drug solids. The value of solid state characterizations is stressed but not covered explicitly in this mini-review.

【 授权许可】

Unknown