Preparation and Study of Erythromycin Dry Powder Inhaler Based on Ternary Complex Structure.

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.