Direct compressible polymethacrylic acid-starch compositions for site-specific drug delivery

The purpose of this study was to generate and characterize a direct compressible pH-sensitive excipient composition for controlled drug delivery. In acidic aqueous solutions, polymethacrylic acid (PMAA) forms complexes and precipitates with starch. As the extent of the interaction between PMAA and starch reaches a maximum at a weight ratio of 1:1.38 (PMAA/starch), this composition was used for the direct compression of tablets. These tablets (30 mg) showed no disintegration even after 2 days in a disintegration test apparatus according to the USP XXIII, in simulated gastric fluid at pH 1.2. In contrast, in 100 mM phosphate buffer pH 7.0 they disintegrated within 40.25+/-8.42 min (mean+/-S.D., n=3). Control tablets of starch disintegrated within the first minute at both pH values. Dissolution studies with the model peptide peroxidase demonstrated no release within 120 min at pH 1.2, whereas at pH 7.0, 100% of the peptide was released within 330 min. Similar release profiles were obtained with the model drugs amoxicillin and rifampicin. In addition, the use of a PMAA-starch composition as a carrier matrix for peroxidase and amoxicillin provided a protective effect towards pepsin and hydrolytic degradation at pH 1.2, respectively. According to these results, the PMAA-starch composition may be a useful tool to overcome the very harsh environment of the stomach for future delivery systems.