甲硝唑固体分散体的制备及痤疮洗剂的质量改进

Preparation of Acne Lotion Containing A Metronidazole Solid Dispersion Formulation

目的制备甲硝唑固体分散体并建立其中甲硝唑的含量测定方法，将该固体分散体作为制备痤疮洗剂的中间体，以提高原有洗剂当中甲硝唑的溶解度。方法分别以聚乙二醇10000、聚乙二醇6000为载体，采用熔融法制备了甲硝唑固体分散体，进行X-射线粉末衍射分析以鉴别药物在不同载体中的分散状态，比较筛选出形成固体分散体的理想载体材料并制备固体分散体洗剂，采用紫外分光光度法，检测波长为316．0nm，测定固体分散体以及洗剂当中甲硝唑的含量。结果甲硝唑以无定型状态存于聚乙二醇10000中，而以晶体形式存在于聚乙二醇6000中，甲硝唑-聚乙二醇10000固体分散体洗剂为澄清溶液，甲硝唑浓度在5～13μg/mL范围内与吸光度呈良好线性关系（r=0．9999），平均回收率为99．76％，RSD为0．14％（n=9）。结论熔融法成功制备了甲硝唑-聚乙二醇10000固体分散体，制备工艺简单易行、成本较低，固体分散技术能够显著提高甲硝唑的溶解度和制剂的稳定性，含量测定方法稳定、快速、准确、简便，可以作为甲硝唑-聚乙二醇10000固体分散体以及痤疮洗剂中甲硝唑的质量控制方法。

Objective To prepare metronidazole solid dispersion; to establish a method for the determination of metronidazole in the solid dispersion; to use the solid dispersion as an intermediate to prepare acne lotion for improving the dissolubility of metronidazole in the previous lotion. Methods Metronidazole solid dispersions were prepared with PEG10 000 and PEG6 000 as carriers by melting method respectively. Powder X-ray diffractometry was used to identify the state of the drug in the 2 carriers. The most ideal carrier was used to prepare solid dispersion lotion. Ultraviolet spectrometry was used to measure the content of metronidazole in the solid dispersion and the lotion with detective wavelength at 316.0 nm. Results Metronidazole was dispersed amorphously in PEG10 000 but existed as crystal in PEG6 000. The improved lotion was plained solution. The calibration curve was linear in the range of 5 - 13 p.g/mL （ r = 0. 999 9 ） for metronidazole. The average recovery was 99.76 % with RSD 0.14% （n = 9）. Conclusion Metronidazole-PEGl0 000 sohd dispersion has been prepared successfully by melting method. The procedure is simple, available and economic. The technology of solid dispersion is potent in improving the dissolution of metronidazole and the stability of the lotion. The UV method is reproducible, rapid, accurate, simple, and is suitable for the quality control of metronidazole in the PEG10 000 solid dispersion and ache lotion.