title: pH-independent release of a weakly basic drug from water-insoluble and -soluble matrix tablets.
abstract: Weakly basic drugs or salts thereof demonstrate pH-dependent solubility. The resulting release from conventional matrix tablets decreases with increasing pH-milieu of the gastrointestinal tract. The aim of this study was to overcome this problem and to achieve pH-independent drug release. Two different polymers were used as matrix formers, the water-insoluble and almost unswellable ethylcellulose (EC), and the water-soluble and highly swellable hydroxypropyl methylcellulose (HPMC). Two different approaches to solve the problem of pH-dependent release of weakly basic drugs are demonstrated in this paper. The first one is based on the addition of hydroxypropyl methylcellulose acetate succinate (HPMCAS, an enteric polymer), the second one on the addition of organic acids such as fumaric, succinic or adipic acid to the drug-polymer system. The first approach failed to achieve pH-independent drug release, whereas the addition of organic acids to both matrix formers was found to maintain low pH values within the tablets during drug release in phosphate buffer (pH 6.8 or 7.4). Thus, the micro-environmental conditions for the dissolution and diffusion of the weakly basic drug were almost kept constant. The release of verapamil hydrochloride from tablets composed of ethylcellulose or HPMC and organic acids was found to be pH-independent.
authors.affiliation: College of Pharmacy, Freie Universität Berlin, Kelchstr. 31, 12169, Berlin, Germany.
authors.forename: A
authors.initials: A
authors.lastname: Streubel
authors.forename: J
authors.initials: J
authors.lastname: Siepmann
authors.forename: A
authors.initials: A
authors.lastname: Dashevsky
authors.forename: R
authors.initials: R
authors.lastname: Bodmeier
mesh_terms: D002121:Calcium Channel Blockers / Q000008:administration & dosage* / Q000737:chemistry; D003692:Delayed-Action Preparations; D005079:Excipients; D006863:Hydrogen-Ion Concentration; D008747:Methylcellulose / Q000031:analogs & derivatives; D012995:Solubility; D013607:Tablets; D014700:Verapamil / Q000008:administration & dosage* / Q000737:chemistry; D014867:Water
chemical_list: D002121:Calcium Channel Blockers; D003692:Delayed-Action Preparations; D005079:Excipients; D013607:Tablets; D014867:Water; C048331:hydroxypropylmethylcellulose acetate succinate; D008747:Methylcellulose; D014700:Verapamil