title: An investigation of indomethacin-nicotinamide cocrystal formation induced by thermal stress in the solid or liquid state.
abstract: The impact of thermal stress on indomethacin (IMC)-nicotinamide (NIC) cocrystal formation with or without neat cogrinding was investigated using differential scanning calorimetry (DSC), Fourier transform infrared (FTIR) microspectroscopy, and simultaneous DSC-FTIR microspectroscopy in the solid or liquid state. Different evaporation methods for preparing IMC-NIC cocrystals were also compared. The results indicated that even after cogrinding for 40 min, the FTIR spectra for all IMC-NIC ground mixtures were superimposable on the FTIR spectra of IMC and NIC components, suggesting there was no cocrystal formation between IMC and NIC after cogrinding. However, these IMC-NIC ground mixtures appear to easily undergo cocrystal formation after the application of DSC determination. Under thermal stress induced by DSC, the amount of cocrystal formation increased with increasing cogrinding time. Moreover, simultaneous DSC-FTIR microspectroscopy was a useful one-step technique to induce and clarify the thermal-induced stepwise mechanism of IMC-NIC cocrystal formation from the ground mixture in real time. Different solvent evaporation rates induced by thermal stress significantly influenced IMC-NIC cocrystal formation in the liquid state. In particular, microwave heating may promote IMC-NIC cocrystal formation in a short time.
authors.affiliation: Department of Biotechnology and Pharmaceutical Technology, Yuanpei University, Hsin Chu, 30015, Taiwan, Republic of China.
authors.forename: Hong-Liang
authors.initials: HL
authors.lastname: Lin
authors.forename: Gang-Chun
authors.initials: GC
authors.lastname: Zhang
authors.forename: Yu-Ting
authors.initials: YT
authors.lastname: Huang
authors.forename: Shan-Yang
authors.initials: SY
authors.lastname: Lin
mesh_terms: D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000737:chemistry*; D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D007213:Indomethacin / Q000737:chemistry*; D009536:Niacinamide / Q000737:chemistry*; D017550:Spectroscopy, Fourier Transform Infrared; D013696:Temperature; D014803:Vitamin B Complex / Q000737:chemistry*
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D014803:Vitamin B Complex; D009536:Niacinamide; D007213:Indomethacin
keywords: DSC; DSC-FTIR; physicochemical properties; physical characterization; FTIR; co-crystals; indomethacin; nicotinamide; thermal stress