Fundueanu Gheorghe, Constantin Marieta, Esposito Elisabetta, Cortesi Rita, Nastruzzi Claudio, Menegatti Enea
Department of Pharmaceutical Sciences, University of Ferrara, I-44100 Ferrara, Italy.
Biomaterials. 2005 Jul;26(20):4337-47. doi: 10.1016/j.biomaterials.2004.10.036.
Sulfopropylated dextran microspheres (SP-Ms), (Dm = 80 microm) loaded with a water soluble drug (Tetracycline HCl), were included in cellulose acetate butyrate (CAB) microcapsules. Spherical CAB microcapsules were obtained by oil in water (o/w) solvent evaporation method in the presence of an inert solvent as cyclohexane (CyH) or n-hexane (N-Hex), and different excipients (Phospholipon, Tween, Span, Eudragit RS 100). Chloroform was found to be the best solvent for the preparation of the microcapsules. Also, the sphericity as well as the porosity of the microcapsules was controlled by the presence of an inert solvent. The final concentration of the drug in CAB microparticles was up to 25% (w/w). The key factors for the successful preparation were also the viscosity of the polymer, while the wettability of the resulted microcapsules, the temperature of the preparation, and the porosity have modulated the release of the drug. The higher is the amount of encapsulated microspheres the thinner is the CAB wall between the compartments created by their incorporation. When these microspheres come in contact with the release medium, the pressure created by their swelling breaks the polymer film and the drug starts to be released. The more drug is released in phosphate buffer the higher is the swelling degree of the encapsulated ion exchange resins and the force created by their supplementary swelling will break the more resistants walls. In this way a self-propelled drug release is achieved, until almost all drug was eliberated.
负载水溶性药物(盐酸四环素)的磺丙基化葡聚糖微球(SP-Ms),粒径(Dm = 80微米),被包封于醋酸丁酸纤维素(CAB)微囊中。通过水包油(o/w)溶剂蒸发法,在惰性溶剂如环己烷(CyH)或正己烷(N-Hex)以及不同辅料(磷脂、吐温、司盘、丙烯酸树脂RS 100)存在的情况下,制备得到球形的CAB微囊。已发现氯仿是制备微囊的最佳溶剂。此外,微囊的球形度以及孔隙率可通过惰性溶剂的存在来控制。药物在CAB微粒中的最终浓度可达25%(w/w)。成功制备的关键因素还包括聚合物的粘度,而所得微囊的润湿性、制备温度以及孔隙率则调节了药物的释放。包封的微球数量越多,由其掺入所形成的隔室之间的CAB壁就越薄。当这些微球与释放介质接触时,其溶胀产生的压力会破坏聚合物膜,药物开始释放。在磷酸盐缓冲液中释放的药物越多,包封的离子交换树脂的溶胀程度就越高,其额外溶胀产生的力会破坏更具抗性的壁。通过这种方式实现了自推进式药物释放,直至几乎所有药物都被释放出来。