Study on mechanism for amorphous drug stabilization using gelucire 50/13

Area of Science:

• Pharmaceutical Sciences
• Materials Science

Background:

• Amorphous drug formulations offer enhanced dissolution but face stability challenges due to devitrification.
• Investigating stabilization mechanisms is crucial for expanding the application of amorphous solid dispersions.

Purpose of the Study:

• To investigate the mechanism of amorphous drug stabilization using Gelucire compared to polyvinylpyrrolidone (PVP).
• To evaluate the impact of stabilization techniques on the dissolution and physical state of amorphous celecoxib and etoricoxib.

Main Methods:

• Preparation of amorphous solid dispersions using spray drying and melt-granulation.
• Characterization of drug's physical state via X-ray powder diffractometry and differential scanning calorimetry.
• Assessment of dissolution performance and stability, supported by IR spectroscopy and molecular modeling.

Main Results:

• Melt-granulation significantly improved amorphous celecoxib dissolution compared to amorphous celecoxib and celecoxib-PVP solid dispersions.
• Polyvinylpyrrolidone (PVP) effectively stabilized amorphous celecoxib, while Gelucire showed limited efficacy.
• Hydrogen bonding was identified as the predominant stabilization mechanism, more so than immobilization within a lipid matrix.

Conclusions:

• Melt-granulation with lipids can be more effective for enhancing drug dissolution than simple amorphization.
• The choice of polymer (PVP vs. Gelucire) significantly impacts the stabilization of amorphous drugs, with PVP showing superior performance for celecoxib.
• Hydrogen bonding plays a critical role in the stabilization of amorphous drugs, guiding the development of more stable and effective formulations.