Pulmonary Research Institute of Southeast Michigan, Farmington Hills, MI 48336, USA.
RTI International, Research Triangle Park, NC 27709, USA.
Respir Med. 2018 Jan;134:16-23. doi: 10.1016/j.rmed.2017.09.012. Epub 2017 Sep 25.
Technologies for long-term delivery of aerosol medications in asthma and chronic obstructive pulmonary disease have improved over the past 2 decades with advancements in our understanding of the physical chemistry of aerosol formulations, device engineering, aerosol physics, and pulmonary biology. However, substantial challenges remain when a patient is required to use multiple inhaler types, multiple medications, and/or combinations of medications. Combining multiple drugs into a single inhaler while retaining appropriate dosing of the individual agents in the combination may enhance patient adherence to therapy and reduce device errors that occur when patients are using multiple inhalers. Pressurized metered-dose inhaler (pMDI) devices are widely used by patients for acute symptom relief as well as maintenance treatment, so the pMDI may be a suitable option with which to explore medication combinations. However, optimizing drug formulation remains a key challenge for pMDI delivery systems. This article introduces a new pMDI formulation approach: co-suspension delivery technology, which uses drug crystals with porous, low-density phospholipid particles engineered to deliver combinations of drugs to the airways with accurate and consistent dosing via pMDIs, independent of medication types and combinations. We describe the key characteristics of pMDIs, and discuss the rationale for the co-suspension delivery technology platform based on the limitations associated with traditional formulations. Finally, we discuss the clinical implications of co-suspension delivery technology for developing combination drug therapies administered by pMDIs.
在过去的 20 年中，随着我们对气溶胶制剂的物理化学、装置工程、气溶胶物理学和肺部生物学的理解的进步，用于哮喘和慢性阻塞性肺疾病（COPD）的长期气溶胶药物输送技术得到了改善。然而，当患者需要使用多种吸入器类型、多种药物和/或药物组合时，仍然存在很大的挑战。将多种药物组合到一个单一的吸入器中，同时保持组合中各个药物的适当剂量，可能会提高患者对治疗的依从性，并减少患者使用多个吸入器时发生的装置错误。压力定量吸入器（pMDI）装置被广泛用于急性症状缓解和维持治疗，因此，pMDI 可能是探索药物组合的一个合适选择。然而，优化药物配方仍然是 pMDI 输送系统的一个关键挑战。本文介绍了一种新的 pMDI 配方方法：共悬浮输送技术，该技术使用具有多孔、低密度磷脂颗粒的药物晶体，通过 pMDI 将药物组合准确且一致地输送到气道，而与药物类型和组合无关。我们描述了 pMDI 的关键特性，并根据与传统配方相关的局限性，讨论了共悬浮输送技术平台的基本原理。最后，我们讨论了共悬浮输送技术对通过 pMDI 给药的组合药物治疗的临床意义。
