Solid state characterization of an neuromuscular blocking agent--GW280430A

Area of Science:

• Pharmaceutical Sciences
• Solid-State Chemistry

Background:

• GW280430A is an ultrashort-acting neuromuscular blocking agent used for muscle relaxation during intubation.
• Understanding the solid-state properties of pharmaceutical compounds is crucial for formulation and stability.

Purpose of the Study:

• To conduct a comprehensive solid-state characterization of GW280430A.
• To investigate the influence of water content on the glass transition temperature (Tg) of GW280430A.

Main Methods:

• Differential scanning calorimetry (DSC)
• Thermogravimetric analysis (TGA)
• Powder X-ray diffraction (PXRD)
• Microscopy
• Moisture sorption analysis
• Equilibration over saturated salt solutions

Main Results:

• GW280430A exhibits dehydration at 40°C, glass transition at 130°C, and decomposition at 190°C via DSC.
• PXRD and moisture sorption confirmed GW280430A is amorphous and deliquesces around 70% relative humidity (RH).
• Water acts as a plasticizer, significantly decreasing the Tg of GW280430A as water content increases.

Conclusions:

• GW280430A is an amorphous material whose solid-state properties, particularly its glass transition temperature, are highly sensitive to water content.
• The deliquescent nature and plasticization effect of water on GW280430A are critical considerations for its pharmaceutical formulation and storage.
• No decomposition was observed after storage at 40°C/75% RH for 4 weeks, indicating potential stability under moderate humidity conditions.