Quantitative determination of micronization-induced changes in the solid state of lactose

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Analytical Chemistry

Background:

• α-lactose monohydrate is a key carrier in dry powder inhalers (DPIs).
• Solid-state properties of lactose significantly impact DPI performance.
• Conventional methods like XRPD and DSC may not fully capture processing-induced solid-state changes in lactose.

Purpose of the Study:

• To evaluate the effect of micronization on the solid-state properties of lactose.
• To develop and validate a novel gravimetric method for quantifying different α-lactose forms.
• To investigate the specific forms of α-lactose generated during micronization.

Main Methods:

• X-Ray Powder Diffraction (XRPD) and Differential Scanning Calorimetry (DSC) for initial characterization.
• Development and validation of a new gravimetric method using Dynamic Vapour Sorption (DVS).
• Quantitative analysis of hygroscopic anhydrous, stable anhydrous, and amorphous α-lactose phases.

Main Results:

• XRPD and DSC provided a satisfactory, though not definitive, interpretation of lactose's thermal behavior.
• The novel gravimetric DVS method quantitatively correlates weight changes with specific α-lactose forms.
• The method demonstrated high accuracy for phase quantitation (LODs from 1.6% to 2.7%).
• Application to micronized lactose indicated the generation of hygroscopic anhydrous α-lactose, not amorphous lactose.

Conclusions:

• A novel, simple, and accurate gravimetric method was developed for quantifying hygroscopic anhydrous, stable anhydrous, and amorphous α-lactose.
• Micronization of lactose primarily generates hygroscopic anhydrous α-lactose.
• This method offers a valuable tool for analyzing solid-state changes in lactose and potentially other compounds.