Kadota Kazunori
Laboratory of Formulation Design and Pharmaceutical Technology, Department of Pharmacy, Osaka University of Pharmaceutical Sciences.
Yakugaku Zasshi. 2018;138(9):1163-1167. doi: 10.1248/yakushi.18-00104.
For efficient and deeper drug delivery into the lungs via dry powder inhalers (DPIs), we designed porous spray-dried particles (SDPs) containing anti-tuberculosis drugs and sugar-based excipients. The SDPs were prepared by spray-drying ethanol solutions containing isoniazid and/or rifampicin and sucrose, maltose, or highly branched cyclic dextrin (HBCD). Solid-state fluorescence emission spectroscopy showed that 1-naphthoic acid (1-NPA), a model drug, was dispersed in a molecular dispersion/solid solution, suggesting high potential of HBCD as an excipient in DPIs. 1-NPA was dispersed not only as active pharmaceutical ingredient (API) molecules with HBCD, but also as fine crystals. Morphological examination showed that the fine particles of HBCD/anti-tuberculosis drugs were porous, indicating high aerodynamic performance. Isoniazid and rifampicin could also be incorporated into the HBCD matrix. HBCD formulations exhibited higher released doses and fine-particle fractions than sucrose and maltose formulations, and could incorporate both hydrophilic and hydrophobic drugs.
为了通过干粉吸入器（DPI）实现更高效、更深入的肺部药物递送，我们设计了含有抗结核药物和糖基辅料的多孔喷雾干燥颗粒（SDP）。通过喷雾干燥含有异烟肼和/或利福平以及蔗糖、麦芽糖或高度支化环糊精（HBCD）的乙醇溶液来制备SDP。固态荧光发射光谱表明，模型药物1-萘甲酸（1-NPA）以分子分散/固溶体形式分散，这表明HBCD作为DPI中的辅料具有很大潜力。1-NPA不仅作为活性药物成分（API）分子与HBCD分散在一起，还以细晶体形式存在。形态学检查表明，HBCD/抗结核药物的细颗粒是多孔的，这表明其具有高空气动力学性能。异烟肼和利福平也可以掺入HBCD基质中。与蔗糖和麦芽糖制剂相比，HBCD制剂表现出更高的释放剂量和细颗粒分数，并且可以同时掺入亲水性和疏水性药物。
