Synthesis and Characterization of Novel Polymer-Drug Conjugates Based on the Poly(Styrene-alt-Maleic Anhydride) as a Potential Method for Drug Release

Six well known drugs, captopril, metformin center dot HCl, metroniazole, nortriptyline center dot HCl, fluoxetine center dot HCl and betahistin center dot HCl, were grafted to poly(styrene-alt-maleic anhydride) (PSMA). Grafting was attained by combining of anhydride groups in the PSMA with therapeutic agents containing NH, OH or SH groups. The covalently grafted drugs were identified by infrared, H-1 NMR and UV-Vis spectroscopy. The drug release data at different times fit well to the Korsmeyer-Peppas equation. The analysis of the exponent n of this model revealed a dominant Fickian diffusion mechanism under the in vitro conditions. Furthermore, mean dissolution time values (45.9 to 86.7 h) indicate a high resistance against drugs transport, the highest being obtained for betahistin center dot HCl.