Solubility Temperature Dependence Predicted from 2D Structure

Abstract

The objective of the study was to find a computational procedure to normalize solubility data determined at various temperatures (e.g., 10 -50 o C)

Equilibrium solubility measurement of ionizable drugs – consensus recommendations for improving data quality

“…This example illustrates the need to know the pK a accurately. The value of 4.37 at 37 o C was predicted [26] from the measured value at 25 o C [48]. If 4.37 is the correct value, then the small parallel displacement of the solubility values in the pH [4][5] region to lower pH is consistent with the presence of half-ionized aggregates, [AH.…”

“…Concomitantly, Baka et al [3] examined the classical saturation shake-flask method, to assess which experimental conditions significantly affect the measured equilibrium solubility. More recently, solubility data quality has been reviewed by Avdeef [4].…”

“…Several excellent books and reviews serve as background material for the commentary covering the solubility of druglike molecules: general coverage of solubility [7][8][9][10]; salt formation/selection [11][12][13][14][15][16]; polymorphism [17][18][19][20]; analysis of saturated solution speciation [21][22][23][24][25][26][27]; dissolution/solubility of cocrystals [28][29][30][31][32][33][34][35][36][37]; anhydrous forms versus hydrates [16,38,39].…”

Phenothiazines solution complexity – Determination of pKa and solubility-pH profiles exhibiting sub-micellar aggregation at 25 and 37°C

“…The three least soluble drugs have the highest heats of dissolution: ∆H sol 0 = 152, 134, 99 kJ·mol -1 for chlorpromazine, triflupromazine, and trifluoperazine, respectively. The last column in Table 4 lists the predicted values of enthalpy of solution, based on a multiple linear regression model, trained with 626 molecules (Avdeef, 2015b). It is interesting to note that the above three least-soluble phenothiazines have the highest discrepancies between measured and calculated enthalpies.…”

“…Almost all values were reported near room temperature (20-25 o C), with the exception of fluphenazine, which was only available at 37 o C. Table 5 summarizes the comparisons and Figure 5 displays the correlation between the values reported here and the averaged values from the literature. Before averaging the room temperature results, all room temperature values were transformed to a common 25 o C basis using a recently described procedure (Avdeef, 2015b), to match the temperature in the study here. Figure 5 shows nearly perfect agreement for fluphenazine, promazine, and triflupromazine.…”