Dry powder inhaler formulation.
Dry powder inhaler formulation.
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DOI：
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发表时间：
2005-09
期刊：
影响因子：
2.5
通讯作者：
M. Telko;A. Hickey
中科院分区：
文献类型：
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作者：
M. Telko;A. Hickey
药物产品结合了药理活性和药物特性。理想的性能特征是物理和化学稳定性、易于加工、准确和可重现地递送至靶器官以及在作用部位的可用性。对于干粉吸入器（DPI），这些目标可以通过合适的粉末制剂、有效的计量系统和仔细选择的装置来满足。本次审查的重点是DPI的制定和发展过程。大多数DPI制剂由与较大载体颗粒混合的微粉化药物组成，其增强流动性，减少聚集，并有助于分散。固有物理化学性质、粒度、形状、表面积和形态的组合影响相互作用力和空气动力学性质，这反过来又决定了流化、分散、递送至肺部和在外周气道中的沉积。当DPI被启动时，制剂被流化并进入患者的气道。在吸气气流的影响下，药物颗粒与载体颗粒分离并被携带深入肺部，而较大的载体颗粒冲击口咽表面并被清除。如果作用在粉末上的内聚力太强，则气流的剪切可能不足以将药物与载体颗粒分离，这导致低沉积效率。对气溶胶和固态物理学以及界面化学的理解的进步正在将配方开发从经验活动转变为基础科学基础。
A drug product combines pharmacologic activity with pharmaceutical properties. Desirable performance characteristics are physical and chemical stability, ease of processing, accurate and reproducible delivery to the target organ, and availability at the site of action. For the dry powder inhaler (DPI), these goals can be met with a suitable powder formulation, an efficient metering system, and a carefully selected device. This review focuses on the DPI formulation and development process. Most DPI formulations consist of micronized drug blended with larger carrier particles, which enhance flow, reduce aggregation, and aid in dispersion. A combination of intrinsic physicochemical properties, particle size, shape, surface area, and morphology affects the forces of interaction and aerodynamic properties, which in turn determine fluidization, dispersion, delivery to the lungs, and deposition in the peripheral airways. When a DPI is actuated, the formulation is fluidized and enters the patient's airways. Under the influence of inspiratory airflow, the drug particles separate from the carrier particles and are carried deep into the lungs, while the larger carrier particles impact on the oropharyngeal surfaces and are cleared. If the cohesive forces acting on the powder are too strong, the shear of the airflow may not be sufficient to separate the drug from the carrier particles, which results in low deposition efficiency. Advances in understanding of aerosol and solid state physics and interfacial chemistry are moving formulation development from an empirical activity to a fundamental scientific foundation.