Development of controlled drug release systems based on thiolated polymers

The purpose of the present study was to generate mucoadhesive matrix-tablet s based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was t hereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcel lulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/ -84 mu mol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aq ueous solutions these modified polymers were capable of forming inter- and/ or intramolecular disulfide bonds. The velocity of this process augmented w ith increase of the polymer- and decrease of the proton-concentration. The oxidation proceeded more rapidly within thiolated PCP than within thiolated CMC. Due to the formation of disulfide bonds within thiol-containing polym ers, the stability of matrix-tablets based on such polymers could be strong ly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and P CP remained stable for 6.2 h (mean, n=4) and more than 48 h, respectively. Release studies of the model drug rifampicin demonstrated that a controlled release can be provided by thiolated polymer tablets. The combination of h igh stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery sy stems. (C) 2000 Elsevier Science B.V. All rights reserved.