Green Synthesis of Ibuprofen–Nicotinamide Cocrystals and In-Line Evaluation by Raman Spectroscopy

Abstract

Pharmaceutical cocrystals are mixed crystals that contain two or more different molecular components. These crystals usually present different characteristics from their precursor, an improvement in the drug solubility being the most important property. This article is the first to report a green synthesis of ibuprofen–nicotinamide cocrystal in aqueous media. The use of safer solvents and in-line monitoring are some of the green chemistry principles that should be evaluated in environmentally correct synthesis. The Raman spectroscopy as a PAT tool provided an effective in line method to monitor and quantify the reaction. This is the first report of the cocrystal of ibuprofen–nicotinamide obtained by slurry conversion. A total conversion of the initial substrates into the cocrystal was obtained in mild conditions. The use of chemometric tools and Raman spectroscopy made it possible to monitor and understand the cocrystallization mechanism, and the synthesis provided.