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 《-》

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》

Pharmaceutical characterisation and evaluation of cocrystals: Importance of in vitro dissolution conditions and type of coformer.

The objectives of this study were to demonstrate the importance of experimental set-up and type of coformer for the enhanced dissolution properties of cocrystals. Carbamazepine-saccharin and carbamazepine-nicotinamide cocrystals were prepared by the sonic slurry method and characterised with SEM, DSC, XRPD and particle size analysis. Solubility and dissolution testing (closed and open system) were performed in compendial media and media with a physiologically relevant amount of surfactant. Carbamazepine cocrystals (1:1 molar ratio) did not show a difference in the equilibrium solubility compared to the carbamazepine in compendial media but a substantial difference was observed in modified media. In compendial media, a faster dissolution rate was obtained only from the carbamazepine-saccharin cocrystal, whereas in modified media both cocrystals had a substantial higher dissolution compared to carbamazepine. With the selected method a clear difference in the dissolution profiles of each cocrystal is shown, driven by the characteristics of the coformer used. This study demonstrated that improved dissolution of carbamazepine from the cocrystal forms can be revealed only by appropriate selection of in vitro conditions. The characteristics of the coformer define a critical variable for dissolution of pharmaceutical cocrystals with important implications for their in vivo performance.

Tomaszewska I ，Karki S ，Shur J ，Price R ，Fotaki N ... -  《-》

A novel strategy for pharmaceutical cocrystal generation without knowledge of stoichiometric ratio: myricetin cocrystals and a ternary phase diagram.

Hong C ，Xie Y ，Yao Y ，Li G ，Yuan X ，Shen H ... -  《-》

Crystallization pathways and kinetics of carbamazepine-nicotinamide cocrystals from the amorphous state by in situ thermomicroscopy, spectroscopy, and calorimetry studies.

The work presented here was motivated by the premise that the amorphous state serves as a medium to study cocrystal formation. The molecular mobility inherent to amorphous phases can lead to molecular associations between different components such that a single crystalline phase of multiple components or cocrystal is formed. Cocrystallization pathways and kinetics were investigated from amorphous equimolar phases of carbamazepine and nicotinamide using hot-stage polarized microscopy (HSPM), hot-stage Raman microscopy (HSRM), differential scanning calorimetry (DSC), and X-ray powder diffraction (XRPD). Nonisothermal studies revealed that amorphous phases generate cocrystals and that thermal history affects crystallization pathways in significant ways. Two different pathways to cocrystal formation from the amorphous phase were identified: (1) at low heating rates (3 degrees C/min) a metastable cocrystalline phase initially nucleates and transforms to the more stable cocrystalline phase of CBZ-NCT, and (2) at higher heating rates (10 degrees C/min) individual components crystallize, then melt and the stable cocrystalline phase nucleates and grows from the melt. Isothermal studies above the T(g) of the amorphous equimolar phase also confirm the nucleation of a metastable cocrystalline phase from the amorphous state followed by a solid phase mediated transformation to the stable cocrystalline phase. Cocrystallization kinetics were measured by image analysis and by thermal analysis from small samples and are described by the Avrami-Erofeev model. These findings have important implications for the use of amorphous phases in the discovery of cocrystals and to determine the propensity of cocrystallization from process-induced amorphization.

Seefeldt K ，Miller J ，Alvarez-Núñez F ，Rodríguez-Hornedo N ... -  《JOURNAL OF PHARMACEUTICAL SCIENCES》