Characterization of Amorphous Ibrutinib Thermal Stability

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Chemical Engineering

Background:

• Drug amorphization is crucial for enhancing solubility and bioavailability.
• Selecting appropriate amorphization techniques requires considering drug properties and scalability.
• Amorphous solid dispersions often require excipients to improve stability and performance.

Purpose of the Study:

• To compare various amorphization techniques for preparing amorphous ibrutinib.
• To investigate the impact of amorphization methods on the physicochemical properties, stability, and degradation of ibrutinib.
• To explore the role of temperature in controlling ibrutinib's solubility, permeability, and degradation product formation.

Main Methods:

• Melt quench
• Hot melt extrusion
• Solvent evaporation
• Ball milling
• Lyophilization
• Physicochemical characterization
• Stability studies
• Zimm plot analysis

Main Results:

• Temperature significantly influences ibrutinib solubility and permeability, mediated by a degradation product.
• The degradation product has the potential to polymerize, increasing molecular weight.
• Amorphization temperature controls the quantity, polymerization rate, and structure of the impurity.
• Zimm plot analysis was used to determine the molecular weight of the degradation product, a novel application for this class of molecules.

Conclusions:

• The choice of amorphization method and process parameters, particularly temperature, critically affects the quality and stability of amorphous ibrutinib.
• Understanding and controlling degradation pathways is essential for developing stable amorphous drug formulations.
• This study provides novel insights into the characterization and control of impurities in amorphous pharmaceuticals.