Aerosol Research Laboratory, Tehran University of Medical Sciences, Iran.
Int J Nanomedicine. 2010 Oct 5;5:763-70. doi: 10.2147/IJN.S12415.
This study concerns the supercritical antisolvent process which allows single-step production of 5-fluorouracil (5-FU) nanoparticles. This process enhances the physical characteristics of 5-FU in order to deliver it directly to the respiratory tract. Several mixtures of methanol with dichloromethane, acetone, or ethanol were used for particle preparation, and their effects on the physical characteristics of the final products were studied. The conditions of the experiment included pressures of 100 and 150 bar, temperature of 40°C, and a flow rate of 1 mL/min. The particles were characterized physicochemically before and after the process for their morphology and crystallinity. In spite of differences in size, the particles were not very different regarding their morphology. The resulting particles were of a regular shape, partly spherical, and appeared to have a smooth surface, whereas the mechanically milled particles showed less uniformity, had surface irregularities and a high particle size distribution, and seemed aggregated. Particles of 5-FU precipitated from methanol-dichloromethane 50:50 had a mean particle size of 248 nm. In order to evaluate the aerodynamic behavior of the nanoparticles, six 5-FU dry powder formulations containing mixtures of coarse and fine lactose of different percentages were prepared. Deposition of 5-FU was measured using a twin-stage liquid impinger and analyzed using a validated high pressure liquid chromatography method. Addition of fine lactose improved the aerodynamic performance of the drug, as determined by the fine particle fraction.
本研究涉及超临界抗溶剂过程，该过程可一步生产 5-氟尿嘧啶（5-FU）纳米颗粒。该过程增强了 5-FU 的物理特性，以便将其直接递送至呼吸道。使用甲醇与二氯甲烷、丙酮或乙醇的几种混合物来制备颗粒，并研究了它们对最终产物物理特性的影响。实验条件包括 100 和 150 巴的压力、40°C 的温度和 1 毫升/分钟的流速。在该过程前后，对颗粒的形态和结晶度进行了物理化学性质的表征。尽管粒径存在差异，但颗粒的形态差异不大。所得颗粒形状规则，部分呈球形，表面似乎光滑，而机械研磨的颗粒则不太均匀，表面不规则，粒径分布较宽，似乎团聚。从甲醇-二氯甲烷 50:50 中沉淀的 5-FU 颗粒的平均粒径为 248nm。为了评估纳米颗粒的空气动力学行为，制备了六种包含不同比例粗乳糖和细乳糖混合物的 5-FU 干粉制剂。使用双级液体冲击器测量 5-FU 的沉积，并使用经过验证的高压液相色谱法进行分析。细乳糖的添加改善了药物的空气动力学性能，这是由细颗粒分数决定的。
