Preparation and characterization of amorphous amphotericin B nanoparticles for oral administration through liquid antisolvent precipitation

• Published in: European journal of pharmaceutical sciences 2014-03, Vol.53, p.109-117
• Main Authors: Zu, Yuangang, Sun, Wei, Zhao, Xiuhua, Wang, Weiguo, Li, Yong, Ge, Yunlong, Liu, Ying, Wang, Kunlun
• Format: Article
• Language: English
• Subjects: Administration, Oral; Amphotericin B; Amphotericin B - chemistry; Antifungal Agents - chemistry; Characterization; Chemical Precipitation; Dimethyl Sulfoxide - chemistry; Drug Compounding - methods; Freeze Drying; LAP; Nanoparticles; Nanoparticles - chemistry; Oral; Poloxamer - chemistry; Polysorbates - chemistry; Preparation; Solubility; Solvents - chemistry; Surface-Active Agents - chemistry; Temperature
• ISSN: 0928-0987; 1879-0720
• DOI: 10.1016/j.ejps.2013.12.005

In order to improve the solubility of its oral drug deliver system, amphotericin B (AmB) nanoparticles were prepared by liquid antisolvent precipitation, followed by freeze-drying. The amorphous AmB nanoparticles were obtained with MPS of 135.1nm. The AmB nanoparticles exhibit 2.1 times faster dissolution rate and 13 times equilibrium solubility compared with raw drug. AmB nanoparticles show the potential of improving its oral absorption. [Display omitted] We prepared amphotericin B (AmB) nanoparticles through liquid antisolvent precipitation (LAP) and by freeze-drying to improve the solubility of AmB for oral administration. The LAP was optimized through a single-factor experiment. We determined the effects of surfactants and their concentration, the stirring time, the precipitation temperature, the stirring intensity, the drug concentration and the volume ratio of antisolvent to solvent on the mean particle size (MPS) of the AmB nanoparticles. Increased stirring intensity and precipitation time favored AmB nanoparticles with smaller MPS, but precipitation times exceeding 30min did not further reduce the MPS. Increased Tween-80 concentration and the drug concentration decreased the MPS of the AmB nanoparticles. Increased precipitation temperature and antisolvent to solvent volume ratio initially decreased the MPS of the AmB nanoparticles, which increased thereafter. Optimum conditions produced AmB nanoparticles with an MPS of 135.1nm. The AmB nanoparticles were characterized through scanning electron microscopy (SEM), mass spectrometry (MS), Fourier transform infrared spectroscopy (FTIR), X-ray diffraction (XRD), differential scanning calorimetry (DSC), thermal gravimetric analysis (TG), solvent residue, drug purity test, and dissolution testing. The analyses indicated that the chemical structure of AmB remained unchanged in the nanoparticles, but the structure was changed from crystalline to amorphous. The residual DMSO in the nanoparticles was 0.24% less than the standard set by the International Conference on Harmonization limit for class III solvents. The AmB nanoparticles exhibited 2.1 times faster dissolution rates and 13 times equilibrium solubility compared with the raw drug. The detection results indicate that the AmB nanoparticles potentially improved the oral absorption of AmB.