Compositions of Highly Dispersed Silica with Trypsin and a Cationic Surfactant Obtained by a Mechanosorption Method

Abstract

Powdered drug preparations usually appear as mechanical mixtures of parent compounds with inert fillers, ground down to micron particle size. The process of dispersing solid substances is one of the major processing stages in drug fabrication technology. This processing significantly modifies the physicochemical properties of substances and, as a rule, considerably increases their specific surface areas. The process of joint milling usually not only distributes the parent compound between filler particles but leads to their mutual adsorption as well. Being simple and technologically flexible, the method of adsorption immobilization is a promising approach to creating combined drug preparations. An additional advantage is the absence of foreign substances, which considerably simplifies toxicological testing of the products. Previously [1, 2] it was established that the adsorption of the proteolytic enzyme trypsin on the surface of a highly dispersed silica (Aerosil) from an aqueous medium leads to partial loss of the catalytic activity of the enzyme. At the same time, it was shown [3] that the cationic surfactants ethonium and decamethoxine lead to a significant stabilization of trypsin and chymotrypsin in solution, but the mechanism of this effect is still incompletely clear. The purpose of this work was to study the effect of cationic surfactants on the stability of trypsin comminuted jointly with a highly dispersed silica in a ball mill, with a view to the development of a technology for enzyme-containing drug compositions. The experiments were performed with commercial crystalline trypsin (Rudikom, Kiev) possessing a specific activity of not less than 10 TUg (TU = tyrosine unit of activity); a highly dispersed silica in the form of Aerosil A-300 grade (Khlorvinyl Corporation, Kalush, Ukraine); and pharmacopoeial preparations of ethonium and decamethoxine. The mixtures were mechanically treated in a ball mill with a drum volume of 0.9 dm 3 operating at a drum rotation speed