Chemiadsorbates of p-hydroxybenzoic acid methyl ester on silica as a new type of pro-drug. III. Modeling and simulation of drug release from chemiadsorbates to acid aqueous solution

Abstract

The in vitro release of physi- and chemiadsorbates of p-hydroxybenzoic acid methyl ester (PHBAME) on a colloidal (Aerosil 0 × 50; BET surface 50 m 2 g −1) and a porous silica support (KG 100; mean pore size 10 nm, BET surface 300 m 2 g −1) in an acidic dissolution fluid was investigated and the release kinetics described by mathematical modeling with an analog-hybrid computer. The release from physiadsorbates on both the colloidal and the porous silica proved to be a fast process, best described by two release constants. The release from the chemiadsorbates, however, is based on different mechanisms: from the plain surface of colloidal silica (fractal dimension 2.0) the drug release can be best described by two hydrolysis reaction rates while four different reaction rates were evaluated for the release of PHBAME from the porous support. From the reaction rates and the activation energies it is concluded that the hydrolysis of the surface link between the PHBAME and the silica surface, the Si-O-c bond is strongly influenced by the surface character of the supports, described by their different fractal dimensions (porous support fractal dimension 2.56).