Abstract
The purpose of this study is to develop novel intestinal-specific drug delivery systems with pH sensitive swelling and drug release properties. Methacrylic-type polymeric prodrugs were synthesized by free radical copolymerization of methacrylic acid, poly(ethyleneglycol monomethyl ether methacrylate) and a methacrylic derivative of N-(4-hydroxyphenyl)-2-(4-methoxyphenyl) acetamide in the presence of ethylene glycol dimethacrylate as crosslinking agent. The effect of copolymer composition on the swelling behavior and hydrolytic degradation were studied in simulated gastric (SGF, pH 1.2) and intestinal fluids (SIF, pH 7.0). The dynamic swelling behavior of these hydrogels was investigated to determine the mechanism of water transport through these hydrogels. The mechanism of water transport through the gels was significantly affected by the pH of the swelling medium and became more relaxation-controlled in a swelling medium of pH 7.0. The swelling and hydrolytic behaviors of hydrogels were dependent on the content of methacrylic acid (MAA) groups and caused a decrease and increase in gel swelling in SGF and SIF, respectively. Drug release studies showed that the increasing content of MAA in the copolymer enhances hydrolysis in SIF. These results suggest that pH-sensitive systems could be useful for preparation of a muccoadhesive system and controlled release of N-(4-hydroxyphenyl)-2-(4-methoxyphenyl) acetamide.