Application And Evaluation Of Hot-melt Granulation Technology In Formulation

In this study, the compositions of empagliflozin and microcrystalline cellulose, and the agomelatine porous adsorbents with crospovidone were prepared by hot-melt granulation technology, and then the technology improving dissolution rate and the preparation of a kind of qualitative state drug were studied.On the aspect of preparation of the compositions of empagliflozin and microcrystalline cellulose, improving dissolution rate, the compositions of empagliflozin were prepared by hot-melt granulation, with microcrystalline cellulose (MCC) as carrier. The ratio empagliflozin to MCC in composition 1,2 and 3 was 1:2, 1:3 and 1:4, respectively. Appearances were observed by microscope; the physical states of compositions were investigated by differential scanning calorimetry (DSC) and X-ray powder diffraction analysis (PXRD). The dissolution rate of empagliflozin with different particle sizes and different compositions were also compared. The DSC and PXRD spectrums of the compositions showed that empagliflozin existed in amorphous form and crystal form. The dissolution rate of compositions has been improved by hot-melt granulation. The dissolution rate of composition 2 and 3 were similar to that of micronized empagliflozin. It illustrates the dissolution rate of empagliflozin has been improved by hot-melt granulation.On the aspect of preparation of the agomelatine porous adsorbents with crospovidone (PVPP), obtained a kind of stable qualitative state drug, the agomelatine porous adsorbents with crospovidone (PVPP) as carrier were prepared by hot-melt granulation. The porous adsorbents were characterized by power X-ray diffraction (PXRD). Appearances of the prepared porous adsorbents were observed by scanning electron microscope (SEM). The results showed that agomelatine mainly existed as amorphous in porous adsorbents. The solubilities of agomelatine in the adsorbents were increased from 0.27±0.01,0.29±0.00 and 0.30±0.01 mg/mL to 0.40±0.01,0.41±0.02 and 0.40±0.02 mg/mL in pH2.0 hydrochloric acid solution (pH2.0), pH4.5 acetate buffer (pH4.5), and pH6.8 phosphate buffer (pH6.8), respectively. The dissolution rate of adsorbents was faster than agomelatine before 30 min, but became closer after 30 min. The results of assay and impurities indicated that the drug was adsorbed during the preparation of adsorbents, and the impurities were not significantly increased (P>0.05). In addition, the agomelatine porous adsorbent had good physical and chemical stability after storaged for 6 months at 40 ? and the relative humidity of 75%.