Растворимость силденафила цитрата в системах пропиленгликоль-полиэтиленгликоль

Abstract

Исследованы закономерности растворения силденафила цитрата в смесях вода-полиэтиленгликоль с молекулярными массами 200, 400 и 600, полиэтиленгликоль-400 - 1,2-пропиленгликоль, а также подкисленные до рН 4 системы полиэтиленгликоль-400 - 1,2-пропиленгликоль. При подкислении системы ПГ-ПЭГ до рН 4 растворимость силденафила цитрата достигает 24 % масс. Показано, что кривые растворимости в системе ПЭГ-вода хорошо описываются моделью Жуйбана-Акри. Для систем ПГ-ПЭГ-400 предложена модифицированная модель Жуйбана-Акри. На основе оптимального состава смеси растворителей разработана рецептура производства силденафила цитрата в форме спрея.

The aim of the work is to study the dissolution curves of sildenafil citrate in binary media containing polyethylene glycols, to reveal the regularities of dissolution, to select the optimal solvent composition, to develop mathematical models of the process, to develop the sildenafil citrate preparation in a spray form on the basis of the results of studies. The regularities of the dissolution of sildenafil citrate in water-polyethylene glycol mixtures (molecular weights 200, 400, 600) and polyethylene glycol-400 - 1,2-propylene glycol system were investigated. It was found that the solubility curves of the systems studied have an extreme nature. The position of the maximum in the PEG-water systems (80-90 % by weight of PEG) does not depend on the molecular weight of the polymer. In the PG-PEG system, the shift in the position of the maximum to the region of ~ 10% occurs together with a simultaneous increase in the solubility about 2 times in the comparison of water systems. If the PG-PEG-400 system is acidified to pH 4, the solubility of SFC increases, reaching a maximum of 24 % by weight at the point of maximum. It was shown that the solubility curves in the PEG-water system are well described by the Jouyban-Aсree model. For PG-PEG-400 systems, the agreement between the data and the model is unsatisfactory. The modified version of the Jouyban-Aсree was proposed. The degree function of the pair product is the concentration of the components of the solvent mixture used in the modified model. The procedure for calculating of parameters by non-linear least-squares methods with the help of Excel was proposed. The model allows us to describe satisfactorily the solubility of SFC in PG-PEG-400 systems. The formulation of production of sildenafil citrate in the form of a spray based on the optimal composition of the solvent mixture has been developed. The industrial release of the spray is organized.