TY - JOUR
T1 - A New 1:1 Drug-Drug Cocrystal of Theophylline and Aspirin
T2 - Discovery, Characterization, and Construction of Ternary Phase Diagrams
AU - Darwish, Shaza
AU - Zeglinski, Jacek
AU - Krishna, Gamidi Rama
AU - Shaikh, Rahamatullah
AU - Khraisheh, Majeda
AU - Walker, Gavin M.
AU - Croker, Denise M.
N1 - Publisher Copyright:
© 2018 American Chemical Society.
PY - 2018/12/5
Y1 - 2018/12/5
N2 - A new 1:1 drug-drug cocrystal of theophylline (THP) and aspirin (ASP) was successfully prepared by liquid assisted grinding, evaporative crystallization, and slurry conversion crystallization. The obtained cocrystal was comprehensively characterized by single crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, and Fourier transform infrared analysis. Ternary phase diagrams were constructed for the obtained cocrystal in isopropyl alcohol at two different temperatures, i.e., 20 and 40 °C. A narrow stability region was found for the pure THP-ASP cocrystal in the phase diagram at both temperatures. By proper selection of the ratios between THP, ASP, and IPA from the stability region, THP-ASP cocrystals could be purely produced by isothermal slurry conversion in IPA. In addition, molecular modeling was deployed to provide mechanistic insights into the formation of this THP-ASP cocrystal system.
AB - A new 1:1 drug-drug cocrystal of theophylline (THP) and aspirin (ASP) was successfully prepared by liquid assisted grinding, evaporative crystallization, and slurry conversion crystallization. The obtained cocrystal was comprehensively characterized by single crystal X-ray diffraction, powder X-ray diffraction, differential scanning calorimetry, thermogravimetric analysis, scanning electron microscopy, and Fourier transform infrared analysis. Ternary phase diagrams were constructed for the obtained cocrystal in isopropyl alcohol at two different temperatures, i.e., 20 and 40 °C. A narrow stability region was found for the pure THP-ASP cocrystal in the phase diagram at both temperatures. By proper selection of the ratios between THP, ASP, and IPA from the stability region, THP-ASP cocrystals could be purely produced by isothermal slurry conversion in IPA. In addition, molecular modeling was deployed to provide mechanistic insights into the formation of this THP-ASP cocrystal system.
UR - http://www.scopus.com/inward/record.url?scp=85057533989&partnerID=8YFLogxK
U2 - 10.1021/acs.cgd.8b01330
DO - 10.1021/acs.cgd.8b01330
M3 - Article
AN - SCOPUS:85057533989
SN - 1528-7483
VL - 18
SP - 7526
EP - 7532
JO - Crystal Growth and Design
JF - Crystal Growth and Design
IS - 12
ER -