密封组件与配方的相互作用及其对定量吸入器的影响

Interaction between Elastomeric Component and Formulation and Its Influence on Metered Dose Inhalers

定量吸入器(MDI)阀门中的颈垫圈是该容器包装系统的核心组件。当MDI中的液态有机辅料与颈垫圈长期接触后,垫圈的溶胀程度会直接影响环境水分侵入密封系统的速率,并间接影响药物的杂质水平。该研究采用工业计算机断层扫描(CT)技术,检测长期稳定性试验中正置和倒置状态的丙酸倍氯米松吸入气雾剂样品的垫圈溶胀情况,并检测各稳定性试验样品的每揿主药含量、微细粒子剂量、有关物质含量等关键质量属性。结果表明,倒置样品中水解杂质H的含量均明显低于正置样品,颈垫圈与配方的相互作用对泄漏率、毎揿主药含量、微细粒子剂量、每瓶总揿数等其他关键质量属性没有明显影响,均符合《中华人民共和国药典》2020年版标准。

The neck gasket is the core component of the container and closure system for metered dose inhaler(MDI).When the neck gasket has been exposed to the liquid organic excipients for a long time,gasket swelling will directly affect the rate of environmental moisture ingress into the sealing system and indirectly affect the impurity level of the drug.In this study,industrial computerized tomography(CT)technology was used to detect gasket swelling behavior of the marketed beclometasone dipropionate inhalation aerosol samples in the upright and inverted orientations in the long-term stability test,and critical quality attributes such as delivered dose per actuation,fine particles dose(FPD),and related substances were also evaluated.The results showed that the hydrolysis impurity H levels in the inverted stability samples were significantly lower than those of the upright samples in the long-term stability test,and the interaction between neck gaskets and formulations had no obvious effect on other critical quality attributes such as leak rate,delivered dose per actuation,FPD,and medication actuations per container,which were consistent with the standard of the 2020 edition of Chinese pharmacopoeia.