Design of gefitinib-loaded poly (L-lactic acid) microspheres via a supercritical anti-solvent process for dry powder inhalation
Design of gefitinib-loaded poly (L-lactic acid) microspheres via a supercritical anti-solvent process for dry powder inhalation
复制标题
通过超临界反溶剂工艺设计负载吉非替尼的聚（L-乳酸）微球用于干粉吸入
DOI：
10.1016/j.ijpharm.2017.09.051
复制
发表时间：
2017-10-30
影响因子：
5.8
通讯作者：
Jiang, Yanbin
中科院分区：
文献类型：
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作者：
Lin, Qing;Liu, Guijin;Jiang, Yanbin
为了开发更安全、更稳定、更有效的吉非替尼制剂，本研究采用超临界抗溶剂技术制备了聚乳酸L微球。采用优选的OA(16)(4(5))正交表设计对影响因素进行了优化，并用不同的方法对原料和SAS处理后的样品进行了表征。结果表明，所制备的GFB负载的PLLA颗粒呈球形，与原料GFB相比，颗粒尺寸更小、更窄。制备的聚乳酸样品聚集性小，载药量最高(15.82%)，粒径较小(D-50=2.48 PMO，符合干粉吸入器的尺寸要求)。X-射线衍射仪和差示扫描量热仪分析结果表明，GFB以不同于原GFB的晶型形式包覆在PLLA基质中。FT-IR结果表明，经过SAS处理后，GFB的化学结构没有发生变化。体外释放实验结果表明，最佳样品的释药速度慢于GFB原粒。此外，体外抗癌实验结果表明，优化后的样品具有较高的细胞毒性。与过筛乳糖共混后，DPI最佳样品的流动性和气雾化性能得到改善，其休止角为38.4度~23度，微粒含量为63.21%~90%，雾化性能为23.37%~30%。
To develop a safer, more stable and potent formulation of gefitinib (GFB), micro-spheres of GFB encapsulated into poly (L-lactic acid) (PLLA) have been prepared by supercritical anti-solvent (SAS) technology in this study. Operating factors were optimized using a selected OA(16) (4(5)) orthogonal array design, and the properties of the raw material and SAS processed samples were characterized by different methods The results show that the GFB-loaded PLLA particles prepared were spherical, having a smaller and narrower particle size compared with raw GFB. The optimal GFB-loaded PLLA sample was prepared with less aggregation, highest GFB loading (15.82%) and smaller size (D-50 = 2.48 pmo, which meets the size of dry powder inhalers). The results of XRD and DSC indicate that GFB is encapsulated into PLLA matrix in a polymorphic form different from raw GFB. FT-IR results show that the chemical structure of GFB does not change after the SAS process. The results of in vitro release show that the optimal sample release was slower compared with raw GFB particles. Moreover, the results of in vitro anti-cancer trials show that the optimal sample had a higher cytotoxicity than raw GFB. After blending with sieved lactose, the flowability and aerosolization performance of the optimal sample for DPI were improved, with angle of repose, emitted dose and fine particles fractions from 38.4 degrees to 23 degrees, 63.21% to > 90%, 23.37% to > 30%, respectively.