Yang Hongyu, Qin Jianpeng, Wang Yuou, Li Ji, Wang Dongkai
School of Pharmacy, Shenyang Pharmaceutical University, Shenyang, 110016, Liaoning, China.
AAPS PharmSciTech. 2025 May 30;26(5):151. doi: 10.1208/s12249-025-03140-5.
Pulmonary bacterial infections are a common disease, with erythromycin being a first-line treatment. However, conventional erythromycin tablets and injectables exhibit limited therapeutic efficacy and are associated with severe gastrointestinal side effects. Additionally, injectable formulations suffer from poor patient compliance. Dry powder inhaler (DPI) offers superior pulmonary targeting, circumvent first-pass metabolism, and are portable, enhancing patient adherence. In this study, we successfully developed a ternary inhalable erythromycin dry powder formulation (Ery-DPI). The Quality by Design (QbD) approach was employed to establish a design space for erythromycin micronization and to optimize the formulation. The physicochemical properties and fine particle fraction of the erythromycin DPI were evaluated through in vitro experiments. The final formulation, composed of α-lactose, mannitol, and erythromycin in a ratio of 1:0.2:2 (v/v/v), exhibited an FPF of 70 ± 3%. In vivo studies demonstrated that, compared to intravenous administration, Ery-DPI achieved higher and more stable local drug exposure in the lungs. Overall, our study provides new insights into pulmonary drug delivery strategies for treating bacterial infections.
肺部细菌感染是一种常见疾病，红霉素是一线治疗药物。然而，传统的红霉素片剂和注射剂治疗效果有限，且伴有严重的胃肠道副作用。此外，注射剂剂型的患者依从性较差。干粉吸入器（DPI）具有卓越的肺部靶向性，可避免首过代谢，且便于携带，能提高患者的依从性。在本研究中，我们成功研发了一种三元可吸入性红霉素干粉制剂（Ery-DPI）。采用质量源于设计（QbD）方法来建立红霉素微粉化的设计空间并优化制剂。通过体外实验对红霉素DPI的理化性质和细颗粒分数进行了评估。最终制剂由α-乳糖、甘露醇和红霉素按1:0.2:2（v/v/v）的比例组成，其细颗粒分数为70±3%。体内研究表明，与静脉给药相比，Ery-DPI在肺部实现了更高且更稳定的局部药物暴露。总体而言，我们的研究为治疗细菌感染的肺部给药策略提供了新的见解。
