正交实验优化瓜蒌皮微丸的制备工艺及其质量控制研究

Optimization of preparation process of Trichosanthis Pericarpium micro-pills by orthogonal test and quality control study

关键词:  瓜蒌皮微丸  正交实验  质量控制

Key words:  Trichosanthis Pericarpium micro-pill  orthogonal test  quality control

摘要:

[目的]优化瓜蒌皮微丸的制备工艺并建立其质量控制方法。[方法]利用挤出滚圆法制备瓜蒌皮微丸。以微丸的圆整度、Hausner比值、脆碎度及得率为指标，在单因素实验基础上，通过正交实验优化处方制备工艺，并对最佳制备工艺进行验证。根据外观对微丸进行描述，利用化学反应法、薄层色谱法鉴别其中的核苷成分，明确瓜蒌皮微丸的圆整度、含水量、粒径、溶出度等参数水平，同时采用高效液相色谱法对瓜蒌皮微丸中腺苷等5种核苷类成分进行定量分析。[结果]瓜蒌皮微丸处方：润湿剂为水，载药量40%，辅料（微晶纤维素∶淀粉=2∶1）；瓜蒌皮微丸制备的工艺参数：滚圆频率25 Hz，滚圆时间3 min。化学鉴别、薄层鉴别专属性强。瓜蒌皮微丸圆整度、含水量、粒径、溶出度符合2020年版《中华人民共和国药典》规定。10批瓜蒌皮微丸指纹图谱的相似度评价结果均值为0.998 7，相对标准偏差为0.067%；含量测定结果：尿嘧啶38.28 μg/g，黄嘌呤19.34 μg/g，腺苷56.23 μg/g，鸟苷105.46 μg/g，胸苷1.96 μg/g。[结论]瓜蒌皮微丸制备工艺可行，质量控制全面。

Abstract:

[Objective] To optimize the preparation process of Trichosanthis Pericarpium micro-pills pellets and establish a quality control method. [Methods] Trichosanthis Pericarpium micro-pellets were produced by extrusion-spheronisaion method， the roundness， Hausner’ s ratio， friability and yield of the micro-pills were used as indicators. On the basis of single-factor experimental analysis， the prescription preparation process was optimized by orthogonal test and the optimal preparation process was verified. The pellet is described in terms of appearance， and the nucleoside components therein were specified， using chemical reaction method and thin-layer chromatography and the level of parameters such as roundness， water content， particle size and dissolution degree of Trichosanthis Pericarpiu micro-pills were specified. Simultaneously， high-performance liquid chromatography was used to quantitatively analyze more than five nucleoside components， including adenosine， in Trichosanthis Pericarpium micro-pills. [Results] The optimum process for the preparation of Trichosanthis Pericarpium micro-pills：wetting agent was water， loading capacity was 40%， and excipients（microcrystalline cellulose∶starch=2∶1）. The process parameters for preparing Trichosanthis Pericarpium micro-pills were： rounding frequency was 25 Hz， rounding time was 3 min. Chemical identification and thin-layer identification were highly exclusive. The roundness， moisture， particle size and dissolution degree of Trichosanthis Pericarpium micro-pills were in accordance with the 2020 edition of the Chinese Pharmacopoeia. The similarity of the fingerprint profiles of 10 batches of Trichosanthis Pericarpium micro-pills was evaluated with a mean value of 0.998 7， and the relative standard deviation（RSD） was 0.067%. The content determined was 38.28 μg/g for uracil， 19.34 μg/g for xanthine， 56.23 μg/g for adenosine， 105.46 μg/g for guanosine and 1.96 μg/g for thymidine. [Conclusion] The process of preparation of Trichosanthis Pericarpium micro-pills is feasible and the quality control is comprehensive.