Miyamoto Kahori, 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. 2022 Mar 31;14(4):759. doi: 10.3390/pharmaceutics14040759.
Human lung deposition data is non-mandatory for drug approval but very useful for the development of orally inhaled drug products. Lung deposition of inhaled drugs can be quantified by radionuclide imaging, for which one of the first considerations is the method used to radiolabel formulations. In this study, we report the development of a radiolabeling method for lyophilizate for dry powder inhalation (LDPI) formulations. TechneCoat is one method that can radiolabel drug particles without using solvents. In this method, particles are radiolabeled with a dispersion of Tc-labeled nanoparticles called Technegas. Because a LDPI formulation is not comprised of particles but is a lyophilized cake aerosolized by air impact, the TechneCoat method cannot be used for the radiolabeling of LDPI formulations. We therefore modified the TechneCoat apparatus so that LDPI formulations were not aerosolized by the Technegas flow. Radiolabeling using a modified TechneCoat apparatus was validated with model LDPI formulations of interferon alpha (IFN). IFN of Tc-unlabeled, IFN of Tc-labeled, and Tc of Tc-labeled LDPI formulations showed similar behavior, and differences from IFN of Tc-unlabeled LDPI formulations were within ±15% in aerodynamic particle size distribution measurement. Our radiolabeling method for LDPI formulations may be useful for the quantification of drug deposition in human lungs.
人体肺部沉积数据对于药物批准而言并非强制性要求，但对于口服吸入药物产品的研发却非常有用。吸入药物的肺部沉积可通过放射性核素成像进行量化，对此首先要考虑的因素之一是用于对制剂进行放射性标记的方法。在本研究中，我们报告了一种用于干粉吸入冻干制剂（LDPI）的放射性标记方法的开发情况。TechneCoat是一种可在不使用溶剂的情况下对药物颗粒进行放射性标记的方法。在该方法中，颗粒用一种名为Technegas的锝标记纳米颗粒分散体进行放射性标记。由于LDPI制剂并非由颗粒组成，而是通过气流冲击雾化的冻干块，因此TechneCoat方法不能用于LDPI制剂的放射性标记。因此，我们对TechneCoat仪器进行了改进，以使LDPI制剂不会因Technegas气流而雾化。使用改进后的TechneCoat仪器进行放射性标记，通过干扰素α（IFN）的模型LDPI制剂进行了验证。未标记锝的IFN、标记锝的IFN以及标记锝的LDPI制剂中的锝表现出相似的行为，并且在空气动力学粒径分布测量中，与未标记锝的LDPI制剂中的IFN的差异在±15%以内。我们开发的LDPI制剂放射性标记方法可能有助于量化人体肺部的药物沉积。
