In Situ Monitoring of Cocrystallization of Salicylic Acid–4,4′-Dipyridyl in Solution Using Raman Spectroscopy

In situ analysis using Raman spectroscopy was used to monitor the cocrystallization process. Raman spectroscopy in the cocrystallization of acetylsalicylic acid (ASA) and 4,4′-dipyridyl (4DP) in solution was investigated. A 2:1 salicylic acid (SAA)–4DP cocrystal was identified from crystallographic data obtained by X-ray single-crystal diffraction meter. In addition, Raman spectroscopy provided additional information on crystal structure of SAA–4DP cocrystal. Raman spectra peaks of ASA–4DP solution and SAA–4DP cocrystal were observed during crystallization. By the intensity of the peaks selected, nucleation and growth of cocrystal in solution were monitored. As a result, formation of new cocrystal using aspirin and 4DP was successfully monitored by Raman spectroscopy.