ADMET and DMPK, Vol. 7 No. 2, 2019.
Pregledni rad
https://doi.org/10.5599/admet.686
Perspectives in solubility measurement and interpretation
Christel A.S. Bergström
; Department of Pharmacy, Uppsala University, BMC P.O. Box 580, SE-751 23 Uppsala, Sweden
Alex Avdeef
orcid.org/0000-0002-3139-5442
; in-ADME Research, 1732 First Avenue, #102, New York, NY 10128, USA
Sažetak
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.
Ključne riječi
Solubility-pH; shake-flask solubility; intrinsic solubility; thermodynamic solubility; Henderson-Hasselbalch equation; supersaturation; pre-nucleation clusters, drug aggregates; drug salts; pharmaceutical cocrystals
Hrčak ID:
218702
URI
Datum izdavanja:
5.4.2019.
Posjeta: 2.577 *