Determination of partial solubility parameters of five benzodiazepines in individual solvents

Three and Four component partial solubility parameters for diazepam, lorazepam, oxazepam, prazepam and temazepam were determined using the extended and expanded Hansen regression models. A comparison was made also with solubility parameters calculated by the group contribution method proposed by Van Krevelen. Although a limited number of solvents was used, the results from the present study indicate that the partial solubility parameters obtained from the experimental regression models clearly reflect the structural differences in these five structurally related molecules. High R-2-values were observed in the regression models (0.932 less than or equal to R-2 less than or equal to 0.984), except for lorazepam (0.606 less than or equal to R-2 :less than or equal to 0.825). This was attributed to difficulties in obtaining reliable values of the temperature and heat of fusion due to thermal decomposition of this compound. Introduction of the Flory-Huggins size correction parameter did not improve the R-2- and F-values in any of the regression models used. (C) 2001 Elsevier Science B.V. All rights reserved.