The pressure–temperature phase diagram of dimorphic caffeine: experiment versus topology
Abstract
The pressure–temperature behavior of anhydrous caffeine’s two polymorphs—form II (monoclinic) and form I (trigonal)—was characterized by high–resolution powder diffraction, electron microscopy, differential scanning calorimetry and high–pressure thermal analysis. Measured transition enthalpies are 19 J g⁻1 for the solid–solid conversion and 109 J g⁻1 for melting of form I. Direct application of the Clapeyron equation to these state functions yields linear equilibrium relations with slopes of dP/dT =4.15 MPa K⁻1 for the I-II equilibrium and 2.6 MPa K⁻1 for the I–L equilibrium, values that match the direct measurements at different pressures and temperatures in this study and in the literature. The resulting phase diagram shows divergent I-II and I–L lines with increasing pressure, placing caffeine in Bakhuis-Roozeboom’s case 2 (overall enantiotropy) and locating the I–II–L triple point at negative pressure, thus metastable. Form I consistently has a larger specific volume than form II, and the volume change on melting follows the typical VL/VS ratio of about 1.11 for organic solids. The close agreement between experiment and Clapeyron–based (topological) predictions demonstrates that the topological method correctly captures polymorphic stability across broad pressure and temperature ranges.
Related
- Patterning Conductive Aluminium onto Temperature Sensitive Polymers and Tattoo Paper at Room Temperature and Pressure
- Mapping product distribution pathways in liquid-phase furfural hydrogenation: solvent, catalyst, temperature, and pressure effects
- Pressure and temperature dependence of methane pyrolysis and hydrogen production in a micro flow reactor
- Upper Flammability Limits of Methane/Air Mixtures at Elevated Temperature and Pressure
- Hydraulic Pressure and Sintering Temperature and Time Effects on the Performance of Niobium Selenide Designed as Microwave Resonators
BibTeX
@article{barrio2026pressuretemperature,
title = {{The pressure–temperature phase diagram of dimorphic caffeine: experiment versus topology}},
author = {M Barrio and J.-Ll Tamarit and R Ceolin and B Robert and M-A Perrin and Ivo B. Rietveld},
journal = {International Journal of Pharmaceutics},
year = {2026},
month = oct,
doi = {10.1016/j.ijpharm.2026.127455},
url = {https://hal.science/hal-05795391v1},
note = {CC BY 4.0},
}
RIS
TY - JOUR
TI - The pressure–temperature phase diagram of dimorphic caffeine: experiment versus topology
AU - M Barrio
AU - J.-Ll Tamarit
AU - R Ceolin
AU - B Robert
AU - M-A Perrin
AU - Ivo B. Rietveld
PY - 2026
DA - 2026/10/12
JO - International Journal of Pharmaceutics
DO - 10.1016/j.ijpharm.2026.127455
UR - https://hal.science/hal-05795391v1
AB - The pressure–temperature behavior of anhydrous caffeine’s two polymorphs—form II (monoclinic) and form I (trigonal)—was characterized by high–resolution powder diffraction, electron microscopy, differential scanning calorimetry and high–pressure thermal analysis. Measured transition enthalpies are 19 J g⁻1 for the solid–solid conversion and 109 J g⁻1 for melting of form I. Direct application of the Clapeyron equation to these state functions yields linear equilibrium relations with slopes of dP/dT =4.15 MPa K⁻1 for the I-II equilibrium and 2.6 MPa K⁻1 for the I–L equilibrium, values that match the direct measurements at different pressures and temperatures in this study and in the literature. The resulting phase diagram shows divergent I-II and I–L lines with increasing pressure, placing caffeine in Bakhuis-Roozeboom’s case 2 (overall enantiotropy) and locating the I–II–L triple point at negative pressure, thus metastable. Form I consistently has a larger specific volume than form II, and the volume change on melting follows the typical VL/VS ratio of about 1.11 for organic solids. The close agreement between experiment and Clapeyron–based (topological) predictions demonstrates that the topological method correctly captures polymorphic stability across broad pressure and temperature ranges.
SN - 0378-5173
ER -