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Equilibrium solubility measurement of ionizable drugs - consensus recommendations for improving data quality
- Source :
- ADMET AND DMPK, Recercat. Dipósit de la Recerca de Catalunya, instname, Dipòsit Digital de la UB, Universidad de Barcelona, ADMET and DMPK, Volume 4, Issue 2, ADMET and DMPK, Vol 4, Iss 2, Pp 117-178 (2016)
- Publication Year :
- 2016
- Publisher :
- Iapc Publishing, Zagreb, 2016.
-
Abstract
- This commentary addresses data quality in equilibrium solubility measurement in aqueous solution. Broadly discussed is the “gold standard” shake-flask (SF) method used to measure equilibrium solubility of ionizable drug-like molecules as a function of pH. Many factors affecting the quality of the measurement are recognized. Case studies illustrating the analysis of both solution and solid state aspects of solubility measurement are presented. Coverage includes drug aggregation in solution (sub-micellar, micellar, complexation), use of mass spectrometry to assess aggregation in saturated solutions, solid state characterization (salts, polymorphs, cocrystals, polymorph creation by potentiometric method), solubility type (water, buffer, intrinsic), temperature, ionic strength, pH measurement, buffer issues, critical knowledge of the pKa, equilibration time (stirring and sedimentation), separating solid from saturated solution, solution handling and adsorption to untreated surfaces, solubility units, and tabulation/graphic presentation of reported data. The goal is to present cohesive recommendations that could lead to 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.
- Subjects :
- buffer solubility
micelles
Sals
Medicine (miscellaneous)
Bjerrum curve
02 engineering and technology
shake-flask solubility
intrinsic solubility
water solubility
thermodynamic solubility
CheqSol
Potentiometric Cycling for Polymorph Creation
Henderson-Hasselbalch equation
aggregates
oligomers
hydrates
salts
polymorphs
cocrystals
030226 pharmacology & pharmacy
Micelle
Henderson–Hasselbalch equation
03 medical and health sciences
0302 clinical medicine
Organic chemistry
Pharmacology (medical)
General Pharmacology, Toxicology and Pharmaceutics
Solubility
Aqueous solution
Chemistry
lcsh:RM1-950
Solubility equilibrium
021001 nanoscience & nanotechnology
Molar solubility
Hildebrand solubility parameter
lcsh:Therapeutics. Pharmacology
Chemical engineering
Chemistry (miscellaneous)
Ionic strength
Salts
Solubilitat
Henderson-Hasselbalc
0210 nano-technology
Subjects
Details
- ISSN :
- 18487718
- Database :
- OpenAIRE
- Journal :
- ADMET AND DMPK, Recercat. Dipósit de la Recerca de Catalunya, instname, Dipòsit Digital de la UB, Universidad de Barcelona, ADMET and DMPK, Volume 4, Issue 2, ADMET and DMPK, Vol 4, Iss 2, Pp 117-178 (2016)
- Accession number :
- edsair.doi.dedup.....4b319de8a078f91fc9906cdb9bf37fb1