Due to the impact of solid form properties upon bioavailability of drug molecules (APIs), co-crystals another class of crystalline compounds, the Co-crystals, is gaining attention. Co-crystals afford new physicochemical properties to both of the substances which form the co-crystal, what may enable pharmaceutical applications by, for example, increasing the solubility and bioavailability of the API. These multi-component crystals are most typically prepared by mechanochemical methods or by recrystallization from solution. Due to the importance of co-crystals, the objective of this project is the application of chemometric tools for optimization and monitoring of co-crystal synthesis: 1) experimental design in the synthesis of co-crystals in order to minimize cost, waste, and to control the distribution of particle size as function of time; 2) monitoring of the syntheses by in/on/at-line analyses and data evaluation using multivariate exploratory analyses, such as Principal Component Analysis (PCA), in order to evaluate the possibility of applying PAT (Process Analytical Technology) to control synthesis; 3) to develop analytical methods to quantify the yield of co-crystal in the presence of their co-formers using Partial Least Squares (PLS). The following analytical techniques will be used: powder X- ray diffraction (PXRD), Raman spectroscopy, mid and near Infrared (FT-IR and FT-NIR), thermogravimetric analysis (TGA), differential scanning calorimetry (DSC) and particle size analyzers. Hiigh performance liquid chromatography may also be used to evaluate impurities after the synthesis of the co-crystals. Initially, chemometric tools will be employed in the synthesis of citric acid-iso-nicotinamide and resveratrol-caprolactam co-crystals. However, the project will be extended to other APIs and co-formers (e.g. nutraceuticals and peptides) that are being developed in the research group of Professor Michael J. Zaworotko.
News published in Agência FAPESP Newsletter about the scholarship: