For industrial production of cocrystals, screening phase is essential, helping to become the process faster, more effective and efficient, reducing the quantity of reactants used and associated costs. High-throughput screening (HTS) methods can analyze a wide range of compounds simultaneously. As an answer to industrial necessity of more efficient screening methods, different methods must be developed and optimized. Vibrational spectroscopic techniques are fast, non-destructive and non-invasive, do not need pre-treatment of the samples and allow obtaining qualitative and quantitative information. They are useful in cocrystal analysis, once they detect weak interaction as hydrogen bonding, the basis of cocrystal formation. Therefore, its application in the analysis of cocrystal screening methods, together with multivariate analysis, should be studied in detail. For this end, a HTS procedure of hydrochlorothiazide (HTZ) cocrystals is performed using a 96-well plate and ultrasound-assisted cocrystallization. Six coformers were tested considering ratios of HTZ:coformer of 1:1 and 1:2. The cocrystallization products were analyzed by mid infrared spectroscopy and Raman microspectroscopy. Nicotinamide and p-aminobenzoic acid formed cocrystals with HTZ. The systems with arginine showed that the coformer suffered amorphization; however, no proof of the solid state of HTZ was obtained. The results were not conclusive for the system with citric acid. Additionally, in the nicotinamide and citric acid systems, the physical mixture of the plate also reacted without the present of solvent. Overall, the use of mid infrared spectroscopy and multivariate data analysis provided important information on cocrystal formation, purity, and correct ratio assessment.
Keywords: Cocrystals; High-throughput screening; Hydrochlorothiazide; Mid infrared spectroscopy; Raman microspectroscopy.
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