Abstract
The corresponding N-hydroximide and N-methyl-N-hydroximide of poly[ethylene-alt-(maleic anhydride)] (weight average molecular weight (M-w) of 100-500 g mol(-1)) were prepared as a new oral drug delivery system. Syntheses of N-hydroximide and N-methylhydroxamic acid of poly[ethylene-alt-(maleic anhydride)] were carried out by chemical modification of polymer with hydroxylamine and N-methylhydroxylamine, respectively, to give water-soluble polymers. These activated polymers were immobilized with ketoprofen in the presence of dicyclohexylcarbodiimide to give the corresponding water-insoluble ketoprofen conjugates. All products were characterized by elemental analysis as well as Fourier transform infrared and H-1 NMR spectra. In vitro release of ketoprofen was studied by measuring UV absorption at lambda(max) = 260 urn as a function of time. This study demonstrated the potential use of N-hydroximide and N-methyl-N-hydroxamic acid of poly[ethylene-alt-(maleic anhydride)] as a drug delivery system. Controlled release was studied at different pH values and at different temperatures. At physiological temperature, the amount of drug released increased with increasing pH. The copolymer-drug adducts released the drug very slowly at the low pH found in the stomach thus protecting the drug from the action of high acid conditions and resident digestive enzymes. These N-hydroxamic acid polymer-drug conjugates were found to be potentially useful in the delivery of macromolecular drugs to targeted sites in the lower gastrointestinal tract and the colon area. (c) 2007 Society of Chemical Industry.