Milling induced amorphisation and recrystallization of α-lactose monohydrate

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Pharmaceutical powder preprocessing is crucial for manufacturing performance.
• Milling operations can undesirably modify powder properties, impacting processability.
• Controlling material transformations during milling is essential.

Purpose of the Study:

• To evaluate surface and bulk transformations in alpha-lactose monohydrate after milling.
• To investigate the impact of milling duration on lactose amorphicity and structure.
• To compare milled lactose with crystalline and amorphous references.

Main Methods:

• Scanning Electron Microscopy (SEM) and Atomic Force Microscopy (AFM) for morphological analysis.
• AFM with energy dissipation measurements to assess surface amorphicity.
• Differential Scanning Calorimetry (DSC) for bulk material characterization.
• Thermogravimetric Analysis (TGA) to measure water loss.

Main Results:

• Milling induced significant surface amorphicity after 1 hour, with moderate changes at longer durations.
• DSC indicated partial to full amorphicity in milled lactose, with shifted thermal profiles compared to spray-dried amorphous lactose.
• TGA showed lower water content in milled amorphous lactose versus spray-dried amorphous lactose.
• SEM and AFM detected morphological differences between milled and reference lactose samples.

Conclusions:

• Milling promotes surface-to-bulk propagation of amorphicity in alpha-lactose monohydrate.
• Milling results in an amorphous state distinct from spray-dried amorphous lactose.
• The hardened surface post-milling may result from surface crystallization or low-water glass transition.