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Adv Drug Deliv Rev. 2007 Jul 10;59(6):444-53. Epub 2007 May 22.

Production of solid lipid nanoparticle suspensions using supercritical fluid extraction of emulsions (SFEE) for pulmonary delivery using the AERx system.

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Ferro Corporation, Pharmaceutical Technology, 7500 East Pleasant Valley Road, Independence, OH 44131, USA.


The aims of the current work included: development of a new production method for nanoparticles of water-insoluble drugs in combination with lipids, characterization of the nanoparticles and development of lipid nanosuspension formulations, and investigation of the feasibility of delivering the nanosuspensions as aerosols for inhalation using Aradigm's AERx Single Dose Platform (SDP) with micron-sized nozzles and the all mechanical AERx Essence with sub-micron-sized nozzles. The continuous SFEE method was used for particle precipitation of solid lipid nanoparticles (SLN). The method allowed for production of stable particulate aqueous suspensions of a narrow size distribution, with a volume mean diameter below 30 nm (D99% cumulative volume below 100 nm). Thus the particle size obtained was significantly smaller than previously has been achieved by other techniques. The residual solvent content in the final suspension was consistently below 20 ppm. Drug loading values between 10-20% w/w drug were obtained for model compounds ketoprofen and indomethacin in formulation with lipids such as tripalmitin, tristearin and Gelucire 50/13. It was observed that the loading capacity achieved was higher than the thermodynamic limit of the solubility of the drugs in molten lipids. Lipid nanosuspension formulations were successfully aerosolized using both of the AERx systems. As measured by both cascade impactor and laser diffraction, the aerosol fine particle fraction (FPF) was comparable to drug solution formulations typically used in these devices; i.e., greater than 90% of the aerosol mass resided in particles less than 3.5 mum aerodynamic diameter.

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