Nanometer Layer Coating to Lactose Particles for Optimization of Dexamethasone Pulmonary Delivery

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Inhalation Technology

Background:

• Lactose (LA) is a common carrier in dry powder inhalers (DPIs) but suffers from drug adhesion, hindering aerosolization.
• Improving carrier surface properties is crucial for effective DPI formulation and drug delivery.

Purpose of the Study:

• To develop and evaluate surface modification techniques for lactose carriers to enhance DPI performance.
• To investigate the efficacy of Nanometer Layer Coating (NLC) with leucine for improving lactose properties.

Main Methods:

• Four coating methods were assessed: solid mixing, vapor deposition, suspension coating, and solution coating.
• Optimal Nanometer Layer Coating (NLC) using leucine was developed and characterized using SEM, micro-CT, AFM, Raman imaging, FIB-SEM, TOF-SIMS, and XRD.
• Formulations with jet-milled dexamethasone (DEX) were prepared and tested for aerosolization, flowability, and in vivo efficacy.

Main Results:

• Solution coating with leucine resulted in Nanometer Layer Coating (NLC) with continuous nanometer-scale leucine coverage.
• NLC-LA significantly increased the fine particle fraction of dexamethasone from 20% to 50% and improved powder flowability (Carr's Index reduced to 24%).
• In vivo studies showed enhanced bioavailability, enabling a 30-fold dose reduction for dexamethasone DPIs while maintaining therapeutic efficacy in acute lung injury models.

Conclusions:

• Nanometer Layer Coating (NLC) is an effective strategy for modifying lactose carrier surfaces, significantly improving DPI performance.
• This surface engineering approach bridges fundamental science with translational application, advancing inhalation science and formulation development.
• The NLC strategy offers a promising pathway for developing more efficient and effective dry powder inhaler formulations.