Formulation and evaluation of carrier-based dry powders containing budesonide and arformoterol for inhalation therapy

Abstract

ABSTRACT Asthma and Chronic Obstructive Pulmonary Disease (COPD) are major global health issues, with inhalation therapy being a primary treatment method. However, dry powder inhalers (DPIs) often face the issue of drug particle aggregation, which can reduce drug delivery efficiency. This study aims to investigate particle aggregation and optimize the cohesion–adhesion balance to improve inhalation efficiency. Advanced techniques such as atomic force microscopy and Raman imaging were employed to analyze particle interactions and aggregation behavior, focusing on lactose ratios, particle shapes, and drug-drug interactions. The therapeutic efficacy of optimized formulations containing Budesonide (BUD) and Arformoterol (AFT) was evaluated in an asthma model. Specifically, sRAW, neutrophil count, and tidal volume values were significantly improved compared to the positive control group, with p-values below 0.01. AFT demonstrated equivalent efficacy to Formoterol at half the dose. Additionally, pharmacokinetic (PK) studies showed that both drugs exhibited similar in vivo behavior, confirming the therapeutic superiority of AFT. (p-value for AUC0-t and Cmax: 0.646 and 0.153, respectively) The key findings highlight that formulation optimization significantly reduces particle aggregation and improves drug delivery efficiency in DPI (FPF for AFT and BUD: 39.4% and 50.6%, respectively), suggesting the potential for enhanced clinical outcomes in asthma and COPD patients. This study provides valuable insights for the formulation development of inhalable therapies.