Plastic and Glassy Crystal States of Caffeine

Abstract

The present paper focuses on the high temperature form I of caffeine and on its low temperature metastable form. Structural, dynamic, and kinetic information has been obtained by X-ray, dielectric, and calorimetric investigations. This study shows the following features: (1) The high temperature phase (I) of caffeine is in a state of dynamically orientationally disordered crystalline state (so-called "plastic, or rotator, phase"). (2) This high-symmetry hexagonal phase can be maintained at low temperature in a metastable situation. (3) Under deep undercooling of form I a glass transition occurs in the disordered crystalline state near room temperature. It is associated with the orientational freezing in of the molecular motions. Otherwise stated, the metastable state I enters into a nonergodic unstable state, so-called "glassy crystal" state. These findings rationalize the difficulties seen with caffeine in pharmaceutical science.

An investigation into the influence of drug–polymer interactions on the miscibility, processability and structure of polyvinylpyrrolidone-based hot melt extrusion formulations

“…In XRPD diffractograms of HME 20% CAF-PVP, a single characteristic peak at 2θ = 26.86 o was noted which is attributed to metastable Form I CAF (Fig.9d, arrowed) (Descamps and Decroix, 2014). The detection of Form I in the hot processed HME PVP-based extrudates may reflect the enantiotropic nature of this material, with Form I being generated at higher temperatures (Descamps et al, 2005;Descamps and Decroix, 2014;Kishi and Matsuoka, 2010), although clearly the form has persisted on cooling. Since the peaks in the X-ray diffractograms of HME PVP-based CAF systems indicated a different polymorphic form of CAF which was different from the PM of raw CAF, the percentage of CAF crystallinity in the HME extrudates was not calculated.…”

Thermochemical study of two anhydrous polymorphs of caffeine

“…This fact leads Gavezzotti and coworkers to argue that up to now, the failure to obtain an ordered crystal phase, for the lower temperature form of this molecule, is a consequence of its molecular features, namely the existence of an orientational disorder [9]. On the other hand, the structure of the high temperature form (I) was derived from X-ray powder diffraction measurements recorded at 278 K, and it is believed that could be greatly disordered [8,10,11].…”

Predicting the structures and associated phase transition mechanisms in disordered crystals via a combination of experimental and theoretical methods

“…an average "sphere" of electron density at each lattice site. 15 However, the psuedo-order limits the possible degrees of freedom that the molecules within the solid have, enabling more detailed investigation into the bulk structure and dynamics to be performed. 16,17 Because disordered crystals are ultimately disordered, diffraction methods oen rely on other techniques to fully elucidate the static-ordered structures.…”