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目的:确定帕立骨化醇亚微乳注射液的处方和制备工艺。方法:以粒径为评价指标,筛选制备亚微乳的均质压力(700~1 200 bar)和次数(6~14次);以含量为评价指标,筛选亚微乳的pH(4.0~9.0);以外观和杂质总量为评价指标,筛选灭菌温度和时间(115℃、30 min;121℃、15 min;126℃、3 min);以外观、粒径、包封率为评价指标,筛选亚微乳油相的组成[大豆油-中链甘油三酸酯(15∶0~0∶15)]、卵磷脂用量(0.6%~1.8%)、泊洛沙姆188用量(0.2%~0.6%);以Zeta电位和外观为评价指标,筛选油酸钠用量(0~0.1%);以pH和杂质总量为评价指标,筛选维生素E用量(0~0.08%)。按确定的工艺和处方制备的亚微乳注射液,分别在4、25、40℃下放置6个月,观察其理化性质变化。结果:优选处方和工艺为15%油相[大豆油-中链甘油三酸酯(7.5∶7.5)],1.5%卵磷脂,0.5%泊洛沙姆188,0.1%油酸钠,0.08%维生素E,2.25%甘油;均质前调节至pH 8.0,900 bar压力下均质10次,再于121℃灭菌15 min。所制亚微乳注射液在4、25℃下6个月内理化性质各指标无明显变化,40℃下放置6个月样品的pH和Zeta电位略有下降,粒径和总杂质量有所增大。结论:该制剂处方合理,工艺可行,在4~25℃下质量稳定。
Objective: To determine the prescription and preparation of paricalcitol submicroemulsion injection. Methods: The average pressure (700 ~ 1 200 bar) and the number of times (6 ~ 14 times) of preparing submicroemulsion were screened by using the particle size as evaluation index. The content of submicron emulsion ); The total amount of appearance and impurities as the evaluation index, screening sterilization temperature and time (115 ℃, 30 min; 121 ℃, 15 min; 126 ℃, 3 min); appearance, particle size, (Soybean oil-medium chain triglyceride (15: 0-0: 15)], the amount of lecithin (0.6% -1.8%), the amount of poloxamer 188 0.6%); Zeta potential and appearance as the evaluation index, the amount of sodium oleate (0 ~ 0.1%) was screened; the amount of vitamin E (0 ~ 0.08%) was screened by the total amount of pH and impurities. Sub-microemulsion injection prepared according to the established process and prescriptions were respectively placed at 4, 25 and 40 ° C for 6 months to observe the change of their physical and chemical properties. Results: Preferred formulations and processes are 15% oil phase [Soybean Oil - Medium Chain Triglycerides (7.5: 7.5)], 1.5% Lecithin, 0.5% Poloxamer 188, 0.1% Sodium Oleate, 0.08% Vitamin E, 2.25% glycerol; homogenize before adjusting to pH 8.0, homogenize under pressure at 10 bar for 10 times and sterilize at 121 ° C for 15 min. The submicroemulsion injection at 4,25 ℃ within 6 months no significant changes in the physical and chemical properties of indicators, at 40 ℃ for 6 months after the sample pH and Zeta potential decreased slightly, the particle size and the total amount of impurities Increase. Conclusion: The preparation prescription is reasonable, the process is feasible, and the quality is stable at 4 ~ 25 ℃.