Design of gefitinib-loaded poly (L-lactic acid) microspheres via a supercritical anti-solvent process for dry powder inhalation

作者：Lin, Qing; Liu, Guijin; Zhao, Ziyi; Wei, Dongwei; Pang, Jiafeng; Jiang, Yanbin^*

来源：International Journal of Pharmaceutics, 2017, 532(1): 573-580.

DOI：10.1016/j.ijpharm.2017.09.051

• Supercritical anti-solvent process
• Dry powder inhaler
• Lactose
• Two-stage impinger

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.

• 出版日期2017-10-30
• 单位华南理工大学