Miyamoto Kahori, Yanagisawa Misato, Taga Hiroaki, Yamaji Hiromichi, Akita Tomomi, Yamashita Chikamasa
Department of Pharmaceutics and Drug Delivery, Faculty of Pharmaceutical Sciences, Tokyo University of Science, 2641 Yamazaki, Noda, Chiba 278-8510, Japan.
Pharmaceutics. 2021 Apr 29;13(5):632. doi: 10.3390/pharmaceutics13050632.
It has been previously reported that active vitamin D3 (VD3) is a candidate drug that can repair alveolar damage in chronic obstructive pulmonary disease at a very low dose. We herein report the optimization of a very low-dose formulation of VD3 for dry powder inhalation by a simple method based on time-of-flight (TOF) theory. As the preparation content of VD3 is very low, aerodynamic particle size distribution cannot be measured by pharmacopeial methods that require quantification of the main drug. Thus, a simple method based on TOF theory, which can measure aerodynamic particle size distribution without quantification, was used. The optimized formulation for an inhalation system using a lyophilized cake contained phenylalanine as the excipient (VD3 1 μg/vial + phenylalanine 0.3 mg/vial) and showed high performance with fine particle fraction ≤ 3 μm = 47.2 ± 4.4%. The difference between the results of pharmacopeial methods and simple method was examined using the formulation containing 10 µg/vial of VD3 and was within 5.0%. The preparation is expected to efficiently deliver VD3 to the lungs. Our simple method can optimize dry powder inhalation formulations more easily and rapidly even when the content of the main drug in a preparation is very low.
先前已有报道称，活性维生素D3（VD3）是一种候选药物，能够以极低剂量修复慢性阻塞性肺疾病中的肺泡损伤。我们在此报告了一种基于飞行时间（TOF）理论的简单方法，用于优化VD3极低剂量干粉吸入制剂。由于VD3的制剂含量非常低，无法通过需要对主药进行定量的药典方法来测量空气动力学粒径分布。因此，采用了一种基于TOF理论的简单方法，该方法无需定量即可测量空气动力学粒径分布。使用含有苯丙氨酸作为辅料的冻干饼的吸入系统优化制剂（VD3 1μg/瓶 + 苯丙氨酸0.3mg/瓶），并显示出高性能，细颗粒分数≤3μm = 47.2±4.4%。使用含有10μg/瓶VD3的制剂检查药典方法和简单方法结果之间的差异，差异在5.0%以内。该制剂有望将VD3有效地输送到肺部。即使制剂中主药的含量非常低，我们的简单方法也能够更轻松、快速地优化干粉吸入制剂。
