Microstructural Characterization of Dry Powder Inhaler Formulations Using Orthogonal Analytical Techniques.

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Analytical Chemistry

Background:

• Dry powder inhalers (DPIs) require robust analytical methods to assess drug product performance.
• Understanding the impact of material properties and processing on in vivo performance is crucial for locally-acting DPIs.
• Microstructural equivalence of the aerosolized dose is a key factor in DPI efficacy.

Purpose of the Study:

• To explore the utility of Morphologically-Directed Raman Spectroscopy (MDRS) and dissolution as orthogonal techniques.
• To assess the microstructural equivalence of the aerosolized dose of DPIs.
• To understand the impact of material properties and processing on in vivo performance.

Main Methods:

• Commercial DPIs with Fluticasone Propionate (FP) and Salmeterol Xinafoate (SX) were sourced.
• Aerodynamic particle size distribution (APSD), dissolution, and MDRS studies were conducted.
• Principle component analysis was used to identify discriminating agglomerate classes.

Main Results:

• APSD testing alone may not fully explain in vivo performance differences.
• Dissolution studies revealed varying rates between different commercial FP/SX products.
• MDRS results supported dissolution findings, correlating dissolution rate with soluble component fraction.

Conclusions:

• MDRS and dissolution successfully served as orthogonal techniques for analyzing DPI aerosolized doses.
• These in vitro methods provide a valuable link between material attributes/process parameters and in vivo performance.
• Further development of in vitro assessment tools for DPIs is highlighted as important.