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Co-crystals are being studied intensively primarily due to the potential for improved pharmaceutical properties,including the dissolution behavior of BCS class-II drug substances [1,2].Additionally,this approach has been recognized as attractive in terms of new intellectual property,based on the novelty,utility,and non-obviousness of co crystals [3,4].Many reviews and overview articles regarding pharmaceutical co-crystals have been published [5.6].In this study,co-crystal powders of indomethacin and saccharin (IMC-SAC) were prepared by an anti-solvent (water) addition and compared with co-crystals by evaporation method.No successful synthesis of a pharmaceutical co-crystal powder via an anti-solvent approach has been reported.Among solvents examined,methanol was practically the only one that resulted in the formation of highly pure IMC–SAC co-crystal powders by anti-solvent approach.With the ultimate objective of improving pharmaceutical properties of IMC,especially the solubility and dissolution rate,IMC co-crystal was designed and prepared using crystal engineering approaches.X-ray diffraction (XRD) and differential scanning calorimetry (DSC) were performed to characterize the off-line physicochemical properties of co-crystal powders.The morphological and size information was obtained by optical microscopy (OM) and scanning electron microscopy (SEM).The co-crystal powders from anti-solvent crystallization were superior to those from to pure IMC particles and evaporation crystal of the flowability,the solubility and dissolution rate.This key feature might have been associated with the particle size and shape.Also,this mechanism can be explained by the difference solubility of each substance.Accordingly,the anti-solvent approach can be considered as a competitive route for producing pharmaceutical co-crystal powders with acceptable properties.