Stabilization mechanism of limaprost in solid dosage form.

Area of Science:

• Pharmaceutical Science
• Materials Science
• Analytical Chemistry

Background:

• Limaprost degradation by hydrolysis is a critical concern in pharmaceutical formulation.
• Polymeric excipients play a significant role in drug stability, influencing degradation pathways.
• Understanding excipient-drug interactions is essential for developing stable pharmaceutical products.

Purpose of the Study:

• To investigate the impact of various polymeric pharmaceutical excipients on the hydrolytic degradation of limaprost.
• To elucidate the relationship between excipient properties, water mobility, and limaprost stability.
• To identify excipients that enhance the stability of limaprost-alfadex formulations.

Main Methods:

• Utilized near-infrared (NIR) spectroscopy to assess changes in water mobility.
• Employed proton nuclear magnetic resonance (NMR) spin-spin relaxation time (T(2)) measurements to analyze polymer structural relaxation.
• Formulated freeze-dried limaprost-alfadex with different polymeric excipients and exposed them to controlled humid conditions (25°C, 75% RH).

Main Results:

• Cellulose derivatives (HPMC, HPC-L) formulated with limaprost-alfadex showed increased degradation.
• Polysaccharides (dextran40, dextrin, pullulan) suppressed limaprost degradation, despite higher water sorption.
• NIR and NMR data indicated higher water and polymer molecular mobility in HPMC and HPC-L formulations, correlating with accelerated degradation.

Conclusions:

• The molecular mobility of polymeric excipients, particularly cellulose derivatives like HPMC and HPC-L, significantly influences limaprost degradation rates.
• Increased water mobility, associated with higher polymer molecular mobility, accelerates limaprost hydrolysis.
• Polysaccharide excipients demonstrate superior performance in stabilizing limaprost-alfadex against hydrolytic degradation.