Thermal behavior and dynamic fragility in amorphous carisoprodol. Correlation between the dynamic and thermodynamic fragilities

• Published in: Thermochimica acta Vol. 663; pp. 99 - 109
• Main Authors: Diogo, Hermínio P., Ramos, Joaquim J. Moura, Piedade, M. Fátima M.
• Format: Journal Article
• Language: English
• Published: Elsevier B.V 10-05-2018
• Subjects: Carisoprodol; DSC; Molecular mobility; Polymorphism; TSDC; TSDC; Carisoprodol; DSC; Molecular mobility; Polymorphism
• ISSN: 0040-6031; 1872-762X
• DOI: 10.1016/j.tca.2018.03.012

[Display omitted]
•A polymorph of carisoprodol was first discovered and characterized by DSC and XRPD.•The molecular mobility in amorphous carisoprodol was characterized by DSC and TSDC.•The dynamic and thermodynamic fragilities were compared for a large number of glass forming drugs.•The reduced glass transition temperature was found to be 0.72, significantly higher than the “2/3 rule” value.
The polymorphism in carisoprodol was analyzed, and a metastable polymorph, B, was detected for the first time whose melting enthalpy was estimated, and which showed a monotropic relationship with the most stable polymorph, A. A third crystalline form was sometimes observed in small quantities, with a melting temperature very close to that of B. Polymorph A melted at Tfus = 95 °C (ΔHfus = 38 kJ mol−1); on the other hand carisoprodol showed a strong glass forming ability with a glass transition temperature Tg = −8 °C, meaning that it can exist as a metastable liquid at room temperature; furthermore, it crystallizes isothermally at room temperature over long periods, and exhibits cold crystallization at about 60 °C when heated on slow ramps. The molecular mobility of the amorphous solid state of carisoprodol was characterized by its steepness (or fragility) index, m, and by the activation energy at Tg, Ea(Tg), determined from the heating rate dependence of the temperature location of the DSC glass transition signature as well as from the features of the TSDC peak of the glass transition. Finally, the dynamic fragility measured for carisoprodol and for a wide range of other drugs and small molecule glass-forming liquids, was compared with the thermodynamic fragility as defined by Wang and Angell. The comparison showed a reasonable agreement, and it was found that the most probable value of the reduced glass transition temperature is 0.73, somewhat different from that corresponding to the “2/3 rule”.