title: Development of controlled drug release systems based on thiolated polymers.
abstract: The purpose of the present study was to generate mucoadhesive matrix-tablets based on thiolated polymers. Mediated by a carbodiimide, L-cysteine was thereby covalently linked to polycarbophil (PCP) and sodium carboxymethylcellulose (CMC). The resulting thiolated polymers displayed 100+/-8 and 1280+/-84 micromol thiol groups per gram, respectively (means+/-S.D.; n=6-8). In aqueous solutions these modified polymers were capable of forming inter- and/or intramolecular disulfide bonds. The velocity of this process augmented with 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 polymers, the stability of matrix-tablets based on such polymers could be strongly improved. Whereas tablets based on the corresponding unmodified polymer disintegrated within 2 h, the swollen carrier matrix of thiolated CMC and PCP 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 high stability, controlled drug release and mucoadhesive properties renders matrix-tablets based on thiolated polymers useful as novel drug delivery systems.
authors.affiliation: Institute of Pharmaceutical Technology, Center of Pharmacy, University of Vienna, Althanstr. 14, A-1090, Vienna, Austria. andreas.bernkop-schuerch@univie.ac.at
authors.forename: A
authors.initials: A
authors.lastname: Bernkop-Schnürch
authors.forename: S
authors.initials: S
authors.lastname: Scholler
authors.forename: R G
authors.initials: RG
authors.lastname: Biebel
mesh_terms: D000180:Acrylic Resins; D000269:Adhesives; D000327:Adsorption; D002266:Carboxymethylcellulose Sodium; D003545:Cysteine / Q000737:chemistry; D003692:Delayed-Action Preparations; D004220:Disulfides / Q000737:chemistry; D004337:Drug Carriers; D005612:Freeze Drying; D006863:Hydrogen-Ion Concentration; D009092:Mucous Membrane; D010592:Pharmaceutic Aids; D011108:Polymers / Q000737:chemistry*; D012293:Rifampin / Q000737:chemistry; D012995:Solubility; D013438:Sulfhydryl Compounds / Q000737:chemistry*; D013608:Tablets, Enteric-Coated; D014867:Water
chemical_list: D000180:Acrylic Resins; D000269:Adhesives; D003692:Delayed-Action Preparations; D004220:Disulfides; D004337:Drug Carriers; D010592:Pharmaceutic Aids; D011108:Polymers; D013438:Sulfhydryl Compounds; D013608:Tablets, Enteric-Coated; D014867:Water; C030312:calcium polycarbophil; D002266:Carboxymethylcellulose Sodium; D003545:Cysteine; D012293:Rifampin