Abstract: The purpose of this study was to improve the dispersion and bioavailability of altrenogest (ALT) in water. The solvent method (ethyl cellulose, hydroxypropyl methyl cellulose, lactose) and solvent-melt method (polyethylene glycol 6000, glycerin monostearate, lactose) were used to preparation the ALT solid dispersions and sustained-release silicone suppository. The linearity, stability of the solid dispersion, precision of the instrument and the recovery rate of the standard were investigated. Fourier transform infrared spectroscopy (FTIR) and microscope were used to observe and analyze its apparent morphology. The sustained-release degree of ALT in 14 d was measured by sustained-release test. The results showed that ALT had a good linear relationship (R²=0.9996) in the concentration range of 1~12 μg/mL, and the instrument precision was good (RSD=0.48%). The stability of ALT solid dispersion prepared by solvent method and solvent-melt method was good, with RSD of 0.57% and 0.58%, respectively. The variation between the spiked recovery data of ALT solid dispersion prepared by solvent method and solvent-melt method was small, and the recovery rate was high. Infrared spectra and microscope images of active agent and solid dispersions showed that ALT solid dispersion was formed. The optimal combination of solvent method to prepare ALT solid dispersion was ethyl cellulose:hydroxypropyl methyl cellulose:lactose=1:0.6:1:6. The optimal combination of solvent-melt method to prepare ALT solid dispersion was PEG6000:glycerol monostearate:lactose=1:10:1.5:6. The sustained-release experiments of the sustained-release silicone suppositorials prepared by solvent method and solvent-melt method showed that the concentration of altrenogest increased gradually from 0-48 h, and reached the peak value of 37.73 and 30.46 μg/mL at 144 and 48 h, respectively, and then remained above 21 and 13 μg/mL, respectively. By comparison, the sustained release effect of the solid dispersion of ALT prepared by solvent method was better than that prepared by solvent-melt method, and the preparation method of the solid dispersion of ALT was simple, and the used carrier materials were non-toxic, which provided a reference basis for the further application of the solid dispersion in vivo.

Key words: altrenogest; preparation of solid dispersion; release degree; Fourier transform infrared spectroscopy (FTIR); microscopic imaging