Rzewińska Aleksandra, Szlęk Jakub, Dąbrowski Damian, Juszczyk Ewelina, Mróz Katarzyna, Räikkönen Heikki, Siven Mia, Wieczorek Maciej, Dorożyński Przemysław
Finished Dosage Forms Department, Research and Development Center, Celon Pharma S.A., Marymoncka 15, 05-052 Kazuń Nowy, Poland.
Department of Drug Technology and Pharmaceutical Biotechnology, Faculty of Pharmacy, Medical University of Warsaw, Banacha 1, 02-097 Warszawa, Poland.
Pharmaceutics. 2024 Aug 31;16(9):1157. doi: 10.3390/pharmaceutics16091157.
The pursuit of targeted therapies for cytokine-dependent diseases has led to the discovery of Janus kinase (JAK) inhibitors, a promising class of drugs. Among them, CPL409116, a selective dual JAK and rho-associated protein kinase inhibitor (ROCK), has demonstrated potential for treating conditions such as pulmonary fibrosis exacerbated by the COVID-19 pandemic. This study investigated the feasibility of delivering CPL409116 via inhalation, with the aim of minimizing the systemic adverse effects associated with oral administration. Two micronization methods, jet milling and spray drying, were assessed for CPL409116, with spray drying chosen for its ability to produce an amorphous form of the compound. Moreover, parameters such as the mixing energy, drug load, and force control agent significantly influenced the fine particle fraction (FPF), a critical parameter for pulmonary drug delivery. This study provides insights into optimizing the formulation parameters to enhance the delivery efficiency of CPL409116 to the lungs, offering potential for improved therapeutic outcomes in cytokine-dependent pulmonary diseases.
对细胞因子依赖性疾病靶向治疗方法的探索促使人们发现了一类前景广阔的药物——Janus激酶（JAK）抑制剂。其中，CPL409116作为一种选择性双JAK和rho相关蛋白激酶抑制剂（ROCK），已显示出治疗因COVID-19大流行而加重的肺纤维化等病症的潜力。本研究探讨了通过吸入方式递送CPL409116的可行性，目的是尽量减少与口服给药相关的全身不良反应。针对CPL409116评估了两种微粉化方法，即气流粉碎和喷雾干燥，最终选择喷雾干燥是因为它能够制备该化合物的无定形形式。此外，混合能量、药物负载量和力控制剂等参数对细颗粒分数（FPF）有显著影响，而细颗粒分数是肺部药物递送的关键参数。本研究为优化制剂参数以提高CPL409116向肺部的递送效率提供了见解，为改善细胞因子依赖性肺部疾病的治疗效果带来了潜力。
