Raman and terahertz spectroscopical investigation of cocrystal formation process of piracetam and 3-hydroxybenzoic acid

• Raman and THz-TDS spectra of piracetam and its pharmaceutical cocrystal formed with 3-hydroxybenzoic acid are reported.
• The piracetam cocrystal formation process is monitored from both Raman and THz-TDS spectra.
• THz-TDS is potential to directly characterize the pharmaceutical cocrystal reactions in solid-state.

Cocrystallization can improve physical and chemical properties of active pharmaceutical ingredient, and this feature has great potential in pharmaceutical development. In this study, the cocrystal of piracetam and 3-hydroxybenzoic acid under grinding condition has been characterized by Raman and terahertz spectroscopical techniques. The major vibrational modes of individual starting components and cocrystal are obtained and assigned. Spectral results show that the vibrational modes of the cocrystal are different from those of the corresponding parent materials. The dynamic process of such pharmaceutical cocrystal formation has also been monitored directly with Raman and THz spectra. The formation rate is pretty fast in first several 20 min grinding time, and then it becomes slow. After ∼35 min, such process has been almost completed. These results offer us the unique means and benchmark for characterizing the cocrystal conformation from molecule-level and also provide us rich information about the reaction dynamic during cocrystal formation process in pharmaceutical fields.

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