Amorphous solid dispersions containing residual crystallinity: Influence of seed properties and polymer adsorption on...

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Amorphous solid dispersions (ASDs) enhance drug solubility through supersaturation.
• Crystallinity in ASDs negates solubility benefits and can trigger drug precipitation.
• Understanding residual crystal impact is crucial for ASD performance.

Purpose of the Study:

• To investigate the effect of residual crystals on the supersaturation profiles of indomethacin-copovidone (PVPVA) ASDs.
• To assess the role of PVPVA as a crystallization inhibitor in the presence of indomethacin seeds.
• To identify risk factors associated with residual crystallinity in ASDs.

Main Methods:

• Manufacturing of indomethacin-copovidone ASDs with varying residual crystallinity via hot melt extrusion (HME).
• Characterization of residual crystals using atomic force microscopy (AFM) and scanning electron microscopy (SEM).
• Non-sink dissolution testing to evaluate supersaturation and desupersaturation profiles.

Main Results:

• PVPVA demonstrated significant inhibition of indomethacin nucleation and crystal growth at high supersaturation levels.
• ASDs with 0-25% residual crystallinity exhibited reduced solubility advantage and minimal desupersaturation.
• Polymer adsorption onto residual crystals was observed, leading to "poisoned" crystal growth.

Conclusions:

• Residual crystals in ASDs diminish the solubility advantage.
• PVPVA effectively inhibits indomethacin crystallization, mitigating the negative impact of residual seeds.
• Key risk factors include polymer inhibition efficacy, seed characteristics, and supersaturation conditions.