Preparation Of Ultrafine Azithromycin By Liquid Precipitation And Investigation Of Their Properties

Azithromycin (AZM), as a new macrolide antibiotic, has been paid increasing attention in clinical application. Due to its poorly water-soluble property, it is difficult to develop the water-soluble formulation of AZM. As a result, the main formulations of AZM used in clinic are oral administration forms. For these forms, the dissolution rate of drug active ingredient in organism determines its bioavailability. Without regard to other effects, the dissolution rate of drug solid mainly depends on the BET surface area of the drug particles with a direct contact with the solvent. Therefore, it is an effective method for increasing the solubility of AZM to decrease the drug particle size and improve its BET surface area through micronization.In this study, ultrafine AZM particles were successfully prepared by liquid precipitation method. The experimental conditions for the anti-solvent precipitation and the reactive precipitation were systematically investigated. Subsequently, the anti-solvent precipitation process was successfully scaled up in the continuous Rotating Packed Bed (RPB). Finally, in vitro dissolution properties of AZM crude particles and ultrafine samples were tested. The experimental results indicated that the ultrafine AZM particles with a size ranging from0.5to1.0μm could be prepared by anti-solvent precipitation method in a beaker. The BET surface area of AZM was increased from0.5878m2/g to11.6062m2/g. In addition, the spherical particles with a size of10-20μm and a second structure were also obtained in this system. The BET surface area reached16.5368m2/g because of the porous structure on the surface. Moreover, the ultrafined AZM particles with the size ranging from300nm to600nm and a BET surface area of16.5301m2/g were prepared by reactive precipitation method. The ultrafine AZM particles obtained by anti-solvent precipitation method in continuous RPB had a smaller particle size, better morphology and structure, and higher BET surface area than those of the products from beaker experiment, displaying the obvious advantages of RPB in the preparation of ultrafined powder.The fourier transform infrared spectroscopy (FT-IR) indicated that no change in chemical structure and composition occurred after micronization. XRD spectrum suggested that the ultrafined AZM particles prepared by anti-solvent precipitation method had the same crystal form with crude particles, while the samples prepared by reactive precipitation method were amorphous. In vitro dissolution tests showed that the dissolution rate of AZM in water was obviously increased after micronization.