Affinity scale between a carrier and a drug in DPI studied by atomic force microscopy

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Surface Chemistry

Background:

• Dry powder inhalers (DPIs) rely on drug-carrier interactions for effective particle adhesion.
• Micronization, a key production step for DPIs, can induce amorphous surfaces on drug particles.
• Relative humidity (RH) significantly influences the amorphous content on drug surfaces, impacting formulation performance.

Purpose of the Study:

• To investigate the surface reactivity, energy, and adhesion forces between lactose (carrier) and zanamivir (drug) crystals under varying RH conditions.
• To evaluate the impact of induced amorphization of the drug surface on its interaction with the carrier.
• To explore the utility of atomic force microscopy (AFM) in characterizing adhesion properties crucial for DPI formulation.

Main Methods:

• Atomic Force Microscopy (AFM) for direct force measurements and surface energy analysis.
• Controlled exposure to various relative humidity (RH) levels to induce surface amorphization.
• Comparative analysis of adhesion forces between crystalline and amorphous drug forms with the carrier.

Main Results:

• Amorphization of the zanamivir drug surface led to a notable increase in its affinity for the lactose carrier.
• Both ex situ and in situ amorphization of zanamivir resulted in adhesion affinities comparable to those between raw materials (carrier and micronized drug).
• AFM successfully discriminated adhesion forces between different drug particle forms, highlighting its potential for DPI formulation analysis.

Conclusions:

• Drug particle amorphization significantly enhances drug-carrier adhesion in DPI formulations.
• AFM is a valuable tool for quantifying adhesion properties and understanding particle interactions in DPIs.
• Controlling drug surface properties, particularly amorphization, is critical for optimizing DPI performance.