目的:研究两种不含防腐剂的甲基强的松龙琥珀酸钠(MTPSS)1和10mg/mL滴眼液在90天内的理化和微生物学稳定性,用于治疗Sjögren综合征和干眼综合征等眼病。
方法:两种滴眼液由可注射的MTPSS(Solu-moderin®和Urbason®)制备,注射用水和生理盐水溶液。根据ICH(国际人用药品技术要求协调理事会)指南,然后将它们一式三份储存在冷藏条件下(5±3°C),在室温(25±2°C)下,温度为40°C(±2°C)。根据USP(美国药典),通过HPLC-UV(具有紫外检测的高效液相色谱法)进行活性成分含量的理化控制,以及对pH值的控制,渗透压,和视觉检查。还在冷藏条件下在开放容器中长达30天,在封闭容器中长达90天测试了微生物无菌性。
结果:在5°C下储存的滴眼剂最稳定;在1mg/mL滴眼剂中,从第21天开始,药物的降解率降至90%以下,并且在10mg/mL滴眼液中,从第42天在5°C下储存的制剂中,pH值变化不超过1个单位,与其他配方不同。在任何储存条件下,在第90天,渗透压的变化不超过5%。10mg/mL的非冷冻滴眼剂样品,分别从第14天和第28天呈现白色沉淀。非冷藏的1mg/mL滴眼剂在第90天呈现悬浮颗粒。没有颜色变化。微生物分析表明,在密闭容器中无菌保持了90天以上,尽管从第21天开始在开放容器中检测到微生物污染。
结论:1mg/mLMTPSS滴眼液在冷藏下21天显示出物理化学和微生物稳定性,与在相同条件下储存10mg/mL滴眼剂的42天相比。然而,因为它们的组合物中不包含防腐剂,他们不应该使用超过7天打开后。
OBJECTIVE: To study the physicochemical and microbiological stability over 90 days of two preservative-free methylprednisolone sodium succinate (MTPSS) 1 and 10 mg/mL eye drops for use in ocular pathologies such as Sjögren\'s syndrome and dry eye syndrome.
METHODS: The two eye drops were prepared from injectable MTPSS (Solu-moderin® and Urbason®), water for injection and normal saline solution. In accordance with ICH (International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use) guidelines, they were then stored in triplicate under refrigerated conditions (5±3 °C), at room temperature (25±2 °C), and at 40 °C (±2 °C). In accordance with the USP (United States Pharmacopeia), physicochemical controls of the active ingredient content were carried out by HPLC-UV (High Performance Liquid Chromatography with Ultraviolet detection), together with controls of pH, osmolality, and visual examination. Microbiological sterility was also tested under refrigerated conditions up to 30 days in open containers and up to 90 days in closed ones.
RESULTS: The eye drops stored at 5 °C were the most stable; in the 1 mg/mL eye drops, degradation of the drug fell below 90% from day 21, and in the 10 mg/mL eye drops, from day 42. pH change did not vary by ≥1 unit in formulations stored at 5 °C, unlike the other formulations. Changes in osmolality did not exceed 5% on day 90 in any storage conditions. Samples of non refrigerate eye drops at 10 mg/mL, presented a white precipitate from day 14 and 28, respectively. Non-refrigerated 1 mg/mL eye drops presented suspended particles on day 90. There were no color changes. Microbiological analysis showed that sterility was maintained for over 90 days in the closed containers, although microbial contamination was detected from day 21 in the open containers.
CONCLUSIONS: 1 mg/mL MTPSS eye drops show physicochemical and microbiological stability for 21 days under refrigeration, compared to 42 days for 10 mg/mL eye drops stored under the same conditions. However, since they do not include preservatives in their composition, they should not be used for more than 7 days after opening.