Equilibrium solubility measurement of ionizable drugs - consensus recommendations for improving data quality
2016
Authors
Aydeef, AlexFuguet, Elisabet
Llinas, Antonio
Rafols, Clara
Bosch, Elisabeth
Volgyi, Gergely
Verbić, Tatjana
Boldyreva, Elena
Takacs-Novak, Krisztina
Article (Published version)
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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 pK(a), equilibration time (stirring and sedimentation), separating solid from saturated solution, solution handling and adsorption to untreated surfaces, solu...bility 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.
Keywords:
shake-flask solubility / intrinsic solubility / water solubility / buffer solubility / thermodynamic solubility / Bjerrum curve / CheqSol / Potentiometric Cycling for Polymorph Creation / Henderson-HasselbalcSource:
ADMET AND DMPK, 2016, 4, 2, 117-178Publisher:
- Iapc Publishing, Zagreb
DOI: 10.5599/admet.4.2.292
ISSN: 1848-7718
WoS: 000447337700007
Scopus: 2-s2.0-85019028134
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Institution/Community
Hemijski fakultet / Faculty of ChemistryTY - JOUR AU - Aydeef, Alex AU - Fuguet, Elisabet AU - Llinas, Antonio AU - Rafols, Clara AU - Bosch, Elisabeth AU - Volgyi, Gergely AU - Verbić, Tatjana AU - Boldyreva, Elena AU - Takacs-Novak, Krisztina PY - 2016 UR - https://cherry.chem.bg.ac.rs/handle/123456789/2232 AB - 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 pK(a), 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. PB - Iapc Publishing, Zagreb T2 - ADMET AND DMPK T1 - Equilibrium solubility measurement of ionizable drugs - consensus recommendations for improving data quality VL - 4 IS - 2 SP - 117 EP - 178 DO - 10.5599/admet.4.2.292 ER -
@article{ author = "Aydeef, Alex and Fuguet, Elisabet and Llinas, Antonio and Rafols, Clara and Bosch, Elisabeth and Volgyi, Gergely and Verbić, Tatjana and Boldyreva, Elena and Takacs-Novak, Krisztina", year = "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 pK(a), 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.", publisher = "Iapc Publishing, Zagreb", journal = "ADMET AND DMPK", title = "Equilibrium solubility measurement of ionizable drugs - consensus recommendations for improving data quality", volume = "4", number = "2", pages = "117-178", doi = "10.5599/admet.4.2.292" }
Aydeef, A., Fuguet, E., Llinas, A., Rafols, C., Bosch, E., Volgyi, G., Verbić, T., Boldyreva, E.,& Takacs-Novak, K.. (2016). Equilibrium solubility measurement of ionizable drugs - consensus recommendations for improving data quality. in ADMET AND DMPK Iapc Publishing, Zagreb., 4(2), 117-178. https://doi.org/10.5599/admet.4.2.292
Aydeef A, Fuguet E, Llinas A, Rafols C, Bosch E, Volgyi G, Verbić T, Boldyreva E, Takacs-Novak K. Equilibrium solubility measurement of ionizable drugs - consensus recommendations for improving data quality. in ADMET AND DMPK. 2016;4(2):117-178. doi:10.5599/admet.4.2.292 .
Aydeef, Alex, Fuguet, Elisabet, Llinas, Antonio, Rafols, Clara, Bosch, Elisabeth, Volgyi, Gergely, Verbić, Tatjana, Boldyreva, Elena, Takacs-Novak, Krisztina, "Equilibrium solubility measurement of ionizable drugs - consensus recommendations for improving data quality" in ADMET AND DMPK, 4, no. 2 (2016):117-178, https://doi.org/10.5599/admet.4.2.292 . .
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