Study of equilibrium solubility measurement by saturation shake-flask method using hydrochlorothiazide as model compound

2008 ◽  
Vol 46 (2) ◽  
pp. 335-341 ◽  
Author(s):  
Edit Baka ◽  
John E.A. Comer ◽  
Krisztina Takács-Novák
Keyword(s):  
Shake Flask ◽  
Model Compound ◽  
Equilibrium Solubility ◽  
Solubility Measurement

scholarly journals Harmonizing solubility measurement to lower inter-laboratory variance – progress of consortium of biopharmaceutical tools (CoBiTo) in Japan

ADMET & DMPK ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 183-195 ◽  
Author(s):  
Asami Ono ◽  
Naoya Matsumura ◽  
Takahiro Kimoto ◽  
Yoshiyuki Akiyama ◽  
Satoko Funaki ◽  
...  
Keyword(s):  
Shake Flask ◽  
Water Soluble ◽  
Equilibrium Solubility ◽  
Poorly Water Soluble Drugs ◽  
Solubility Measurement ◽  
Water Soluble Drugs ◽  
Poorly Water Soluble ◽  
Proprietary Protocol

The purpose of the present study was to harmonize the protocol of equilibrium solubility measurements for poorly water-soluble drugs to lower inter-laboratory variance. The “mandatory” and “recommended” procedures for the shake-flask method were harmonized based on the knowledge and experiences of each company and information from the literature. The solubility of model drugs was measured by the harmonized protocol (HP) and the non-harmonized proprietary protocol of each company (nonHP). Albendazole, griseofulvin, dipyridamole, and glibenclamide were used as model drugs. When using the nonHP, the solubility values showed large inter-laboratory variance. In contrast, inter-laboratory variance was markedly reduced when using the HP.

scholarly journals Multi-lab intrinsic solubility measurement reproducibility in CheqSol and shake-flask methods

ADMET & DMPK ◽  
2019 ◽  
Vol 7 (3) ◽  
pp. 210-219 ◽  
Author(s):  
Alex Avdeef
Keyword(s):  
Standard Deviation ◽  
Gold Standard ◽  
Shake Flask ◽  
Systematic Errors ◽  
White Paper ◽  
Training Set ◽  
Solubility Measurement ◽  
Correlation Plot ◽  
Measurement Methodology ◽  
Intrinsic Solubility

This commentary compares 233 CheqSol intrinsic solubility values (log S0) reported in the Wiki-pS0 database for 145 different druglike molecules to the 838 log S0 values determined mostly by the saturation shake-flask (SSF) method for 124 of the molecules from the CheqSol set. The range of log S0 spans from -1.0 to -10.6 (log molar units), averaging at -3.8. The correlation plot between the two methods indicates r2 = 0.96, RMSE = 0.34 log unit, and a slight bias of -0.07 log unit. The average interlaboratory standard deviation (SDi) is slightly better for the CheqSol set than that of the SSF set: SDiCS = 0.15 and SDiSSF = 0.24. The intralaboratory errors reported in the CheqSol method (0.05 log) need to be multiplied by a factor of 3 to match the expected interlaboratory errors for the method. The scale factor, in part, relates to the hidden systematic errors in the single-lab values. It is expected that improved standardizations in the ‘gold standard’ SSF method, as suggested in the recent ‘white paper’ on solubility measurement methodology, should make the SDi of both methods be about ~0.15 log unit. The multi-lab averaged log S0 (and the corresponding SDi) values could be helpful additions to existing training-set molecules used to predict the intrinsic solubility of drugs and druglike molecules.

scholarly journals Effects of amount of excess solid, the type of stirring and sedimentation time on solubility of sodium phenytoin and lamotrigine

ADMET & DMPK ◽  
2018 ◽  
Vol 6 (4) ◽  
pp. 269-278 ◽  
Author(s):  
Shahrzad Moattar Mohammadi ◽  
Ali Shayanfar ◽  
Shahram Emami ◽  
Abolghasem Jouyban
Keyword(s):  
Antiepileptic Drugs ◽  
Calibration Curve ◽  
Shake Flask ◽  
Solvent Mixtures ◽  
Solubility Prediction ◽  
Equilibrium Solubility ◽  
Maximum Quantity ◽  
Experimental Works ◽  
Specific Temperature ◽  
Sedimentation Time

Solubility is the maximum quantity of a drug dissolved in a given volume of solvent at a specific temperature. Several factors affect equilibrium solubility. Therefore, different solubility data have been reported for a solute in a certain solvent and temperature in the literature. These variations in solubility are one of the possible reasons for unsuccessful attempts of medicinal chemists for developing models as well as deviation of experimental works for solubility prediction in aqueous, non-aqueous and solvent mixtures. The present research aim is to investigate the effect of the amount of excess solid and the type of stirring on the solubility of drugs. The solubility of two antiepileptic drugs, namely sodium phenytoin and lamotrigine was determined in water, ethanol, and HCl 0.1 M at 37 °C. Different excess amounts of drugs were added to the constant volume of solvent. Additionally, different stirring methods such as magnetic stirrer and shake-flask and sedimentation time were investigated on the solubility values. Saturation solubility of drugs after dilution with water was measured using a spectrophotometer, and the concentration was calculated according to the calibration curve. Amount of excess solid, especially when the drug is in ionized form, and sedimentation time after 24 h have a significant effect on solubility values.

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