摘要
目的制备罗哌卡因-醋酸地塞米松聚乳酸羟基乙酸共聚物(PLGA)微球(简称微球)并研究其体外释药特性。方法以PLGA为载体,采用W1/O/W2双重乳化-溶剂挥发法制备微球,研究实验过程中有机相PLGA浓度、外水相/有机相体积比、内水相体积、外水相聚乙烯醇(PVA)浓度几项因素变化对罗哌卡因-醋酸地塞米松PLGA微球粒径、表面形态、载药量、包封率和突释行为的影响。结果有机相PLGA浓度在制备微球的过程中是一个关键性因素。随着PLGA浓度增加,微球粒径增大,载药量、包封率明显提高,突释降低;外水相/有机相体积比增大,微球粒径增大,载药量、包封率明显提高,微球表面更加光滑、微孔减少,突释降低;随着内水相体积增加使得微球表面的微孔明显增多,突释增加,载药量、包封率降低;当外水相PVA浓度由0.5%增加到2%,微球粒径变小,突释效应增加。通过优化条件制备的微球形状为球形,外观光滑圆整,粒径分布均匀,其中>90%分布在20～70μm。罗哌卡因载药量(7.48±0.33)%,包封率(70.97±2.36)%;醋酸地塞米松载药量(1.52±0.16)%,包封率(57.30±1.17)%。结论采用W1/O/W2双重乳化-溶剂挥发法成功制备罗哌卡因加醋酸地塞米松PLGA微球;以优化工艺制备的微球,在体外具有明显的缓释行为,释药曲线呈典型S形三阶段模式。
Objective To prepare sustained-release PLGA microspheres containing ropicavaine and dexamethasone （Rop- Dex-PLGA-MS） and study drug release in vitro. Methods Rop-Dex-PLGA-MS was prepared with PLGA as cartier by a waterin-oil-in-water（W1/O/W2） duble-emulsion solvent evaporation method. Effects of various preparation parameters, such as polymer concentration, continuous phase/organic phase（CP/OP） ratio, volume of internal water phase and stabilizer PVA concentration on the properties of microspheres, such as particle size, morphology, drug loading, encapsulation efficiency and burst release in vitro were examined. Results PLGA levels was a critical factor for preparing microspheres and particle size; drug loading, encapsulation efficiency were increased significantly with increasing PLGA accompanied by a remarkably decreased burst release. The particles size, drug loading, encapsulation efficiency increased considerably, the surface of microspheres was smoother and burst release decreased as the volume ratio of CP/OP increased. Porous matrix in microspheres augmented, burst release increased and drug loading, encapsulation efficiency decreased with the higher volume of internal water phase. Particle size decreased and burst release increased as PVA concentration in the continuous phase was increased from 0.5% to 2%. By optimizing the prepare technology, Rop-Dex-PLGA-Ms were achieved with spherical shape, smooth surface and evenly distributed. Approximately 90% of microspheres were within the range of 20 - 70 μm in size. The drug loading of ropivacaine and dexamethasone were （7.48 ± 0.33）% and （1.52±0.16）%, and encapsulation efficiencies were （70.97±2.36）% and （57.30±1.17）%, respectively. Conclusion The duble emulsion solvent evaporation method is applicable for preparation of Rop-Dex-PLGA-Ms. The microspheres have a good appearance and significant in vitro sustained-release characteristics as a typical S-shaped and three-phase.
出处
《医药导报》
CAS
2009年第11期1427-1431,共5页
Herald of Medicine
