title: Raman mapping for kinetic analysis of crystallization of amorphous drug based on distributional images.
abstract: The feasibility of Raman mapping for understanding the crystallization mechanism of an amorphous drug was investigated using described images. The crystallization tendency of amorphous indomethacin under dry condition at 30 °C was kinetically evaluated by means of Raman mapping and X-ray powder diffraction (XRPD) with change in the calculated crystallinities. Raman images directly revealed the occurrence of particle size-dependent non-uniform crystallization; slow crystallization of large particles, but fast crystallization of small particles. Kinetic analysis by fitting to the Kolmogorov-Johnson-Mehl-Avrami equation was performed for the crystallization profiles of both Raman mapping and XRPD data. For the Raman mapping data, the distribution of large particles was characterized and examined. The kinetic parameters calculated from the whole Raman image area agreed well with those of XRPD, suggesting accurate prediction of both techniques for the entire crystallization. Raman images revealed the change in the crystallization mechanism for the focused area; the large particles showed a reduced crystallization rate constant and an increase in the dimensional crystal growth exponent. Raman mapping is an attractive tool for quantitative and kinetic investigation of the crystallization mechanism with distributional images.
authors.affiliation: Physicochemical and Preformulation, Applied Chemistry for Drug Discovery, Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan; Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki-shi, Osaka 569-1094, Japan. Electronic address: hiroshi.ueda@shionogi.co.jp.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Ueda
authors.affiliation: Physicochemical and Preformulation, Applied Chemistry for Drug Discovery, Innovative Drug Discovery Research Laboratories, Shionogi & Co., Ltd., 3-1-1, Futaba-cho, Toyonaka-shi, Osaka 561-0825, Japan.
authors.forename: Yasuo
authors.initials: Y
authors.lastname: Ida
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki-shi, Osaka 569-1094, Japan.
authors.forename: Kazunori
authors.initials: K
authors.lastname: Kadota
authors.affiliation: Laboratory of Formulation Design and Pharmaceutical Technology, Osaka University of Pharmaceutical Sciences, 4-20-1, Nasahara, Takatsuki-shi, Osaka 569-1094, Japan.
authors.forename: Yuichi
authors.initials: Y
authors.lastname: Tozuka
mesh_terms: D002152:Calorimetry, Differential Scanning; D003460:Crystallization; D005240:Feasibility Studies; D007213:Indomethacin / Q000737:chemistry*; D007700:Kinetics; D010316:Particle Size; D013059:Spectrum Analysis, Raman / Q000379:methods*; D014961:X-Ray Diffraction / Q000379:methods*
chemical_list: D007213:Indomethacin
keywords: Amorphous drug; Crystallization mechanism; Kinetic analysis; Raman mapping