Advances in Formulation and Technological Strategies for Montelukast Pulmonary Delivery

Le résumé fourni par la source

Montelukast is a leukotriene receptor antagonist used in the management of asthma by modulating airway inflammation. Conventional oral formulations exhibit considerable variation in bioavailability due to extensive first-pass metabolism, short half-life, and wide distribution into peripheral compartments. These limitations, along with systemic adverse effects, challenge consistent therapeutic outcomes. Pulmonary drug delivery has been proposed as a promising alternative by targeting the drug directly to the lungs, potentially bypassing first-pass metabolism and reducing systemic exposure. However, despite extensive research on inhalable montelukast formulations, no product has yet been commercialized. This review discusses the main challenges involved in formulating montelukast for pulmonary administration and highlights recent advances in particle engineering, nanocarriers, and formulation strategies to overcome these limitations. Considering the potential advantages of pulmonary delivery for montelukast, a literature search was conducted to identify inhalable formulations of the drug. Twenty articles were identified, including sixteen on DPIs, one on nebulized montelukast, one on pMDIs and two articles reporting results related to clinical studies of inhaled montelukast. Overall, three clinical studies specifically evaluated inhaled montelukast. No patents evaluating inhaled montelukast were found, although three patents mention inhalation as a possible route without disclosing actual inhaled formulations or device strategies. The available studies were analyzed according to formulation strategies, particle engineering approaches, inhalation devices, and reported outcomes. For DPI formulations, particle aerodynamic diameter plays a critical role in lung deposition, and a mass median aerodynamic diameter (MMAD) in the range of 1-5 μm is generally considered optimal for lung deposition. After deposition, formulation performance depends on an initial burst release followed by sustained drug release, low epithelial permeability, and prolonged pulmonary retention, which are expected to minimize systemic exposure. Overall, the limited number of research highlights a translational gap and important opportunities for the development of inhalable montelukast therapies.

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