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

The purpose of this study was to generate and characterize a direct compres sible pH-sensitive excipient composition for controlled drug delivery. In a cidic aqueous solutions, polymethacrylic acid (PMAA) forms complexes and pr ecipitates with starch. As the extent of the interaction between PMAA and s tarch reaches a maximum at a weight ratio of 1:1.38 (PMAA/starch), this com position was used for the direct compression of tablets. These tablets (30 mg) showed no disintegration even after 2 days in a disintegration test app aratus 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 40.2 5 +/-8.42 min (mean +/-S.D., n = 3). Control tablets of starch disintegrate d within the first minute at both pH values. Dissolution studies with the m odel peptide peroxidase demonstrated no release within 120 min at pH 1.2, w hereas at pH 7.0, 100% of the peptide was released within 330 min. Similar release profiles were obtained with the model drugs amoxicillin and rifampi cin. 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 resu lts, the PMAA-starch composition may be a useful tool to overcome the very harsh environment of the stomach for future delivery systems. (C) 2001 Else vier Science B.V. All rights reserved.