An Investigation of Indomethacin–Nicotinamide Cocrystal Formation Induced by Thermal Stress in the Solid or Liquid State

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 l...

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Bibliographic Details
Published in:Journal of pharmaceutical sciences 2014-08, Vol.103 (8), p.2386-2395
Main Authors: Lin, Hong-Liang, Zhang, Gang-Chun, Huang, Yu-Ting, Lin, Shan-Yang
Format: Article
Language:English
Subjects:
Anti-Inflammatory Agents, Non-Steroidal - chemistry
Calorimetry, Differential Scanning
co-crystals
Crystallization
DSC
DSC-FTIR
DSC‐FTIR
physicochemical properties
physical characterization
FTIR
indomethacin
Indomethacin - chemistry
Niacinamide - chemistry
nicotinamide
physical characterization
physicochemical properties
Spectroscopy, Fourier Transform Infrared
Temperature
thermal stress
Vitamin B Complex - chemistry
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Summary: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. © 2014 Wiley Periodicals, Inc. and the American Pharmacists Association J Pharm Sci 103:2386–2395, 2014
ISSN:0022-3549
1520-6017
DOI:10.1002/jps.24056