Perspectives in solubility measurement and interpretation

• 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.

Ämnesord

MEDICIN OCH HÄLSOVETENSKAP  -- Hälsovetenskap -- Annan hälsovetenskap (hsv//swe)

MEDICAL AND HEALTH SCIENCES  -- Health Sciences -- Other Health Sciences (hsv//eng)

Nyckelord

Solubility-pH

shake-flask solubility

intrinsic solubility

thermodynamic solubility

Henderson-Hasselbalch equation

supersaturation

pre-nucleation clusters

drug aggregates

drug salts

pharmaceutical cocrystals

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