In Situ Cocrystallization of Dapsone and Caffeine during Fluidized Bed Granulation Processing

Area of Science:

• Pharmaceutical Manufacturing
• Materials Science
• Chemical Engineering

Background:

• Pharmaceutical cocrystals offer improved drug properties but scalable manufacturing remains a challenge.
• Existing methods for cocrystal production are often not suitable for large-scale industrial application.
• Dapsone (DAP) and caffeine (CAF) form a stable cocrystal, serving as a model system.

Purpose of the Study:

• To investigate the suitability of fluidized bed granulation for large-scale cocrystal production.
• To explore the mechanism of cocrystallization within a fluidized bed system.
• To assess the impact of process parameters and excipients on cocrystal formation.

Main Methods:

• Cocrystallization via liquid-assisted milling to produce a reference material.
• Fluidized bed granulation of dapsone and caffeine under varied experimental conditions.
• Characterization using differential scanning calorimetry (DSC), X-ray powder diffraction (PXRD), laser diffraction, and scanning electron microscopy (SEM).

Main Results:

• Successful production of dapsone-caffeine cocrystal granules using fluidized bed granulation.
• Cocrystal formation was achieved when dapsone and caffeine were dissolved and sprayed onto fluidized particles.
• The presence of polymers in the spray solution inhibited cocrystallization, leading to amorphization.

Conclusions:

• Fluidized bed granulation is a feasible and effective technique for the large-scale manufacture of pharmaceutical cocrystals.
• Optimizing the liquid phase composition is crucial for successful cocrystallization in this process.
• This method offers a promising alternative for producing cocrystal-based solid dosage forms.