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Preparation of 5-fluorouracil nanoparticles by supercritical antisolvents for pulmonary delivery

Authors Pardis Kalantarian, Abdolhosein Rouholamini Najafabadi, Ismaeil Haririan, et al

Published Date September 2010 Volume 2010:5 Pages 763—770

DOI http://dx.doi.org/10.2147/IJN.S12415

Published 28 September 2010

Pardis Kalantarian1,2, Abdolhosein Rouholamini Najafabadi1, Ismaeil Haririan2, Alireza Vatanara1, Yadollah Yamini3, Majid Darabi1, Kambiz Gilani1
1Aerosol Research Laboratory and 2Pharmaceutical Laboratory, School of Pharmacy, Tehran University of Medical Sciences, 3Department of Chemistry, Tarbiat Modarres University, Tehran, Iran

Abstract: 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.

Keywords: supercritical antisolvent, 5-fluorouracil, lung cancer, nanoparticles

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