D. Vojnovic et D. Chicco, MIXTURE EXPERIMENTAL-DESIGN APPLIED TO SOLUBILITY PREDICTIONS, Drug development and industrial pharmacy, 23(7), 1997, pp. 639-645
The solubility of theophylline (as a model drug) was studied in four-c
omponent systems, using an a priori experimental strategy. Ethanol, po
lyethylenglycol, propylenglycol, and water were chosen as cosolvents.
A reduced cubic model was postulated to describe the solubility as a f
unction of mixture composition. A priori criteria in combination with
an exchange algorithm were used to select, from a set of 31 candidate
points, the optimal design with the least number of experiments. A wei
ghting was assigned to each of the 31 experiments, on the basis of the
cost, in order to obtain a design that would be optimal also from an
economic point of view. Such a methodology made it possible to obtain,
with the minimum number of experiments and with a low cost, a model w
hich was validated and found suitable for accurate prediction of solub
ility.