Synthesis, Characterization, Drug Solubility Enhancement, and Drug Release Study of Poly(Methacrylic Acid-graft-Simvastatin)

Abstract

A series of copolymers were prepared by grafting of simvastatin (SIM) to poly(methacrylic acid) (PMAA) in an esterification reaction with removal water. The resulted copolymers were then crossinlked by using ethylene glycol to form PMAA-graft-SIM hydrogels (SIMA). The FTIR and NMR spectroscopy analyses revealed that the intetramolecular six membered cyclic anhydride units were formed in the PMAA-graft-SIM main chains. The influences of pH media and SIM composition on the retroesterification reaction of SIMA to release SIM were widely investigated. It was observed that the diffusion coefficient of SIM in polymer matrix followed a Fickian model. The kinetic study of SIM released from SIMA films revealed that, at pH 7 (intestines media), SIMA13 showed the higher performance, because this material was capable to release a higher SIM amount (59.00 ± 1.06 wt%) uniformly with a rate of 1.11 ± 0.02 wt%/h during 53 h of the release process. However, this material was capable to release uniformly only a maximum of 9.99 ± 0.09 wt% of SIM at pH 1 (stomach media) during the first 3 h.