Oh Dong-Won, Choi Ji Hoon, Yu Gweon Hee, Kim Bo Kyung, Cho Sang Min, Choi Youn Woong, Jeong Jin-Hyuk, Kang Ji-Hyun, Kim Dong-Wook, Park Chun-Woong
Korea United Pharm R&D Center, Gangnam-gu, Republic of Korea.
Department of Pharmacy, Chungbuk National University, Cheongju, Republic of Korea.
Pharm Dev Technol. 2024 Nov;29(9):966-975. doi: 10.1080/10837450.2024.2413145. Epub 2024 Oct 23.
Asthma and Chronic Obstructive Pulmonary Disease (COPD) are major global health concerns, with inhalation therapy being a primary treatment method. Dry powder inhalers (DPIs) often face challenges related to particle aggregation, which can diminish drug delivery efficiency. This study investigates particle aggregation and aims to optimize the cohesion-adhesion balance to improve inhalation efficiency. Advanced techniques like atomic force microscopy and Raman imaging were used to analyze particle interactions, focusing on lactose ratios, particle morphology, and drug-drug interactions. The therapeutic efficacy of optimized formulations containing budesonide (BUD) and Arformoterol (AFT) was assessed using an asthma model, showing significant improvements in sRAW, neutrophil count, and tidal volume compared to the positive control, with -values below 0.01. AFT exhibited comparable efficacy to Formoterol at half the dose. Additionally, pharmacokinetic studies demonstrated similar in vivo behavior between the drugs, confirming the therapeutic advantage of AFT, with -values for AUC and Cmax of .646 and .153, respectively. The fine particle fractions for AFT and BUD were 39.4% and 50.6%, respectively, indicating improved drug delivery efficiency and potential for better clinical outcomes in asthma and COPD patients.
哮喘和慢性阻塞性肺疾病(COPD)是全球主要的健康问题,吸入疗法是主要的治疗方法。干粉吸入器(DPI)常常面临与颗粒聚集相关的挑战,这可能会降低药物递送效率。本研究调查颗粒聚集情况,旨在优化内聚力 - 附着力平衡以提高吸入效率。使用原子力显微镜和拉曼成像等先进技术分析颗粒相互作用,重点关注乳糖比例、颗粒形态和药物 - 药物相互作用。使用哮喘模型评估含有布地奈德(BUD)和阿福特罗(AFT)的优化制剂的治疗效果,与阳性对照相比,在sRAW、中性粒细胞计数和潮气量方面有显著改善,P值低于0.01。AFT在剂量减半时表现出与福莫特罗相当的疗效。此外,药代动力学研究表明药物之间在体内行为相似,证实了AFT的治疗优势,AUC和Cmax的P值分别为0.646和0.153。AFT和BUD的细颗粒分数分别为39.4%和50.6%,表明药物递送效率提高,对哮喘和COPD患者有更好临床结果的潜力。