Check out a manuscript our scientists published on ternary phase diagram and spray drying of co-crystals

In this work, a ternary phase diagram was developed for a Niclosamide-urea co-crystal (NCS-UR) in isopropanol (IPA) using a combination of slurry and solvent addition methods. The ternary phase diagram showed that solubility of Niclosamide and urea differed by an order of magnitude in IPA, leading to an incongruently saturating system. Spray drying was explored as a method to generate NCS-UR. Co-crystals with small, uniform particle size were successfully prepared by spray drying from equimolar solutions with yield up to 73%. Co-crystals were phase pure by X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) from all conditions explored. Somewhat similar particles were obtained at inlet temperature of 70 °C (mean size of 2.0 μm) compared to 85 °C (2.8-3.4 μm). Based on the TPD, isolating phase pure co-crystal through solution crystallization in IPA would require excess urea. However, spray drying did not require excess co-former. The in-vitro solubility of NCS-UR was compared to anhydrous NCS in biorelevant media. NCS-UR did not give improvement in solubility at 1 h or 24 h. Overall, this work showed that spray drying is a feasible process for preparing phase pure co-crystals for an incongruently saturating system and simultaneously generating micron size particles.