%0 Journal Article
%T Perspectives in solubility measurement and interpretation
%A Avdeef
%A Alex
%A Bergstr£¿m
%A Christel A.S.
%J -
%D 2019
%R 10.5599/admet.686
%X Sa£¿etak 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 ¨C graphically more than mathematically ¨C 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
%K Solubility-pH
%K shake-flask solubility
%K intrinsic solubility
%K thermodynamic solubility
%K Henderson-Hasselbalch equation
%K supersaturation
%K pre-nucleation clusters
%K drug aggregates
%K drug salts
%K pharmaceutical cocrystals
%U https://hrcak.srce.hr/index.php?show=clanak&id_clanak_jezik=319231