Pharmaceutical micro-particles give amorphous sucrose higher physical stability.

Area of Science:

• Pharmaceutical Science
• Materials Science

Background:

• Amorphous solid dispersions are crucial for enhancing drug solubility and bioavailability.
• Maintaining the amorphous state of drugs and excipients is vital for formulation stability.

Purpose of the Study:

• To investigate the impact of micro-sized filler particle properties on the amorphous stability of sucrose.
• To understand how filler characteristics influence the physical stability of amorphous sucrose in freeze-dried composites.

Main Methods:

• Characterization of micro-sized filler particles (crystallinity, hygroscopicity, surface area) using techniques like X-ray diffraction and gas adsorption.
• Preparation of sucrose/filler particle composites via freeze-drying.
• Assessment of composite stability using X-ray diffraction, differential scanning calorimetry (DSC), and microcalorimetry.

Main Results:

• All amorphous composites exhibited enhanced stability compared to pure amorphous sucrose, showing delayed crystallization.
• Filler properties like crystallinity, hygroscopicity, and surface area influenced the stabilization effect.
• Calcium carbonate and oxazepam fillers lost their stabilizing capacity upon humidity exposure.
• Composites displayed higher dry glass transition temperatures (T(g)), indicating reduced molecular mobility.

Conclusions:

• Micro-sized filler particles can improve the physical stability of amorphous sucrose.
• The stabilizing mechanism involves the reduction of molecular mobility within the amorphous phase.
• Filler hygroscopicity and interaction with humidity are critical factors determining long-term amorphous stability in pharmaceutical formulations.