In Situ Cocrystallization via Spray Drying with Polymer as a Strategy to Prevent Cocrystal Dissociation

Area of Science:

• Pharmaceutical Sciences
• Materials Science
• Physical Chemistry

Background:

• Diclofenac acid-l-proline cocrystal (DPCC) exhibits poor physical stability, particularly in humid conditions.
• Cocrystal dissociation poses challenges for drug formulation and delivery.

Purpose of the Study:

• To investigate the impact of various polymers on the dissociation of cocrystals prepared via co-spray-drying.
• To evaluate the physical stability of diclofenac acid-l-proline cocrystal (DPCC) in crystalline solid dispersions (CSDs) with different polymers.

Main Methods:

• Co-spray-drying of API, coformer, and polymer to form CSDs.
• Terahertz Raman spectroscopy (THz Raman) and powder X-ray diffraction (PXRD) for monitoring cocrystal dissociation.
• In situ Raman probe for real-time dissociation monitoring in buffer and water.

Main Results:

• DPCC dissociation is water-mediated, with over 60% dissociation in 18 hours at 40°C and 95% RH.
• Incorporation of 1 wt% polymer into CSDs effectively prevented DPCC dissociation under identical conditions.
• CSDs with polyvinylpyrrolidone (PVP) and poly(1-vinylpyrrolidone-co-vinyl acetate) (PVPVA) demonstrated superior stability, remaining undissociated or partially stable after 7 days.

Conclusions:

• Polymers significantly improve the physical stability of DPCC in CSDs, preventing water-mediated dissociation.
• Spray drying facilitates efficient molecular-level mixing, and in situ polymer gelling forms a protective barrier.
• CSDs with specific polymers like PVP and PVPVA offer enhanced stability and improved dynamic solubility for pharmaceutical applications.