Evaluation of Methyl Methacrylate-Butyl Methacrylate Copolymer Films and Kinetics of Nitrofurazone Release

메칠메타크릴레이트-부틸메타크릴레이트 공중합체 필름의 평가 및 니트로푸라존 방출의 속도론적 연구

Methyl methacrylate-butyl methacrylate copolymer (MMBM)-dibutyl phthalate (DBP) films were investigated as a potential topical drug delivery system for the controlled release of nitrofurazone. The kinetic analysis of release data indicated that drug release followed a diffusion-controlled granular matrix model, where the quantity released per unit area is proportional to the square root of time. DBP of several hydrophobic plasticizers selected was found to give the highest release of nitrofurazone. However, hydrophilic plasticizers such as propylene glycol and polyethylene glycol 400 had no controlled release properties and acceptable film formation. The effects of changes in film composition, drug concentration, film thickness, pH of release medium, and temperature on the in vitro release of nitrofurazone were analyzed both theoretically and experimentally. The release rate constant (k') was found to be proportional to DBP content, pH, and the temperature of release medium, but independent of film thickness, and drug concentration in a range of 0.1-0.4% by weight. The linear relationship was found to exist between the log k' and DBP content. The release of nitrofurazone from MMBM-DBP (8:2) films was found to be an energy-linked process. Two energy terms were calculated ; the activation energy for matrix diffusion was 13.45 kcal/mole, and the heat of drug crystal solvation was 27.26-29.34 kcal/mole. Observation of scanning electron micrographs and microscopic photographs showed that the incorporation of DBP in films increased markedly the particle size of nitrofurazone dispersed in the film matrix, comparing with the fine dispersion of nitrofurazone in pure MMBM film alone.