Ternary Phase Diagram Development and Production of Niclosamide-Urea Co-Crystal by Spray Drying.

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.

MacEachern LA ，Walwyn-Venugopal R ，Kermanshahi-Pour A ，Mirmehrabi M ... -  《-》

Autophagy-Inducing Inhalable Co-crystal Formulation of Niclosamide-Nicotinamide for Lung Cancer Therapy.

Ray E ，Vaghasiya K ，Sharma A ，Shukla R ，Khan R ，Kumar A ，Verma RK ... -  《AAPS PHARMSCITECH》

Generation of 1:1 Carbamazepine:Nicotinamide cocrystals by spray drying.

The present study investigates the potential of spray drying as a technique for generation of pharmaceutical cocrystals. Carbamazepine-Nicotinamide cocrystal (CNC) was chosen as model cocrystal system for this study. Firstly, CNC was generated using liquid assisted grinding and used for generation of phase solubility diagram (PSD) and ternary phase diagram (TPD). Both PSD and TPD were carefully evaluated for phase behavior of CNC when equilibrated with solvent. The undersaturated region with respect to CNC, as depicted by TPD, was selected as target region to initiate cocrystallization experiments. Various points in this region, representative of different compositions of Carbamazepine, Nicotinamide and CNC, were selected and spray drying was carried out. The spray dried product was characterized for solid state properties and was compared with CNC generated by liquid assisted grinding. Spray drying successfully generated CNC of similar quality as those generated by liquid assisted grinding. Moreover, there was no significant impact of process variables on formation of CNC. Spray drying, owing to its simplicity and industrial scalability, can be a promising method for large scale cocrystal generation.

Patil SP ，Modi SR ，Bansal AK 《-》

Spray Drying of Chitosan Acid Salts: Process Development, Scaling Up and Physicochemical Material Characterization.

de la Paz N ，Fernández M ，López O ，Garcia C ，Nogueira A ，Torres L ，Turiño W ，Heinämäki J ... -  《Marine Drugs》

Development and Characterization of Dapsone Cocrystal Prepared by Scalable Production Methods.

do Amaral LH ，do Carmo FA ，Amaro MI ，de Sousa VP ，da Silva LCRP ，de Almeida GS ，Rodrigues CR ，Healy AM ，Cabral LM ... -  《AAPS PHARMSCITECH》