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热熔挤出法制备吲哚美辛共晶及其溶出度研究

陈佳慧, 平其能, 孙敏捷

陈佳慧, 平其能, 孙敏捷. 热熔挤出法制备吲哚美辛共晶及其溶出度研究[J]. 中国药科大学学报, 2019, 50(2): 180-187. DOI: 10.11665/j.issn.1000-5048.20190208
引用本文: 陈佳慧, 平其能, 孙敏捷. 热熔挤出法制备吲哚美辛共晶及其溶出度研究[J]. 中国药科大学学报, 2019, 50(2): 180-187. DOI: 10.11665/j.issn.1000-5048.20190208
CHEN Jiahui, PING Qineng, SUN Minjie. Preparation of indomethacin-nicotinamide cocrystal by hot melt extrusion and its release in vitro[J]. Journal of China Pharmaceutical University, 2019, 50(2): 180-187. DOI: 10.11665/j.issn.1000-5048.20190208
Citation: CHEN Jiahui, PING Qineng, SUN Minjie. Preparation of indomethacin-nicotinamide cocrystal by hot melt extrusion and its release in vitro[J]. Journal of China Pharmaceutical University, 2019, 50(2): 180-187. DOI: 10.11665/j.issn.1000-5048.20190208

热熔挤出法制备吲哚美辛共晶及其溶出度研究

Preparation of indomethacin-nicotinamide cocrystal by hot melt extrusion and its release in vitro

  • 摘要: 为提高吲哚美辛的溶出度,采用热熔挤出法制备吲哚美辛-烟酰胺共晶。以温度和转速为变量考察最佳制备条件,联合热重分析(TGA)、含量测定和有关物质测定评价制备中的热稳定性,通过差示扫描量热法(DSC)、傅里叶红外变换光谱法(FTIR)和粉末X射线衍射法(PXRD)进行物相分析,并评价共晶的溶解度和溶出度优势。结果表明:热熔挤出法在115 ℃下能成功制备吲哚美辛-烟酰胺共晶,在热熔挤出过程中存在低共熔现象,该共晶明显提高了吲哚美辛在各介质中的溶解度、溶出速率和溶出度。通过热熔挤出法制备难溶性药物共晶能明显改善其溶解性,为难溶性药物的开发和共晶技术的发展提供新的思路。
    Abstract: Abstract The indomethacin-nicotinamide cocrystal was prepared by hot melt extrusion(HME)to improve the dissolution of indomethacin in vitro. The optimum preparation conditions were investigated using temperature and rotate speed as variables. Thermogravimetric analysis(TGA), determination of content and determination of related substances were performed to evaluate the thermal stability of indomethacin during the process. Cocrystal was also prepared by solution crystallization from acetonitrile. The products obtained by the two methods were characterized by differential scanning calorimetry(DSC), Fourier transform infrared(FTIR)and powder X-ray diffraction(PXRD). The solubility and dissolution advantages of cocrystal were evaluated. The results showed that the HME method could successfully prepare the indomethacin-nicotinamide cocrystal at 115 °C and eutectic mixture was formed during the process. The cocrystal significantly improved the solubility and dissolution of indomethacin in deionized water, with pH 5. 5 and pH 6. 8 phosphate buffer. The preparation of poorly soluble drug cocrystal by HME can significantly improve its solubility, providing new idea for the development of poorly soluble drugs and HME technology.
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  • 刊出日期:  2019-04-24

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