A simultaneous X-ray diffraction–differential scanning calorimetry study into the phase transitions of mefenamic acid

Abstract

In this study, the polymorphic transitions of mefenamic acid (MA) were studied by synchrotron X‐ray powder diffraction combined with differential scanning calorimetry (XRD‐DSC). The initial material was found to be phase‐pure form I which, when heated, produces two endotherms that can be observed by DSC at 162.72 and 219.55°C. The former was found to correspond to a solid–solid enantiotropic transition from form I to a mixture of forms II and III. The latter is the melting point of form II. As form I is heated, significantly greater unit‐cell expansion is seen in the a direction than in b and c, which can be explained by the stronger intermolecular interactions in the bc plane. Refinements of the reported MA structures against the patterns collected during heating revealed that at 175°C there exists a mixture of forms I, II and III, whereas only forms II and III remain at 205°C. However, reflections are observed at both temperatures which cannot be fitted with the known forms of MA. It is hypothesized that a new form of MA is produced upon heating. The stability of MA after the enantiotropic transition temperature is II > III > I, which differs from the previously reported II > I > III.

Monitoring Polymorphic Phase Transitions in Flufenamic Acid Amorphous Solid Dispersions Using Hyphenated X-ray Diffraction–Differential Scanning Calorimetry

“…The experimental setup for XRD–DSC is very similar to that described in our previous work. 15 XRD–DSC experiments were carried out on the Joint Engineering, Environment and Processing Beamline I12 (JEEP) at the Diamond Light Source. 20 A modified Q20 DSC (TA Instruments) was mounted and aligned on the sample stage in the experimental hutch to allow the monochromated X-ray beam (0.5 mm × 0.5 mm; λ = 0.234 Å) pass through holes in the DSC cell.…”

“…The experimental setup for XRD–DSC is very similar to that described in our previous work . XRD–DSC experiments were carried out on the Joint Engineering, Environment and Processing Beamline I12 (JEEP) at the Diamond Light Source .…”

“…Hyphenating the techniques to obtain DSC and XRD data simultaneously on the same sample has been shown to add significant additional insight. Recently, the combination of high-energy synchrotron XRD with differential scanning calorimetry (XRD−DSC) has been applied to study phase transitions in a range of systems including carbamazepine, 14 mefenamic acid, 15 paracetamol/lactose blends, 16 and spray-dried ASDs of olanzapine. 13 In this paper, ASDs of FFA−polymer were prepared, and the heat-induced crystallization of FFA from the dispersion was explored by XRD−DSC.…”

Metastable crystalline phase formation in deep eutectic systems revealed by simultaneous synchrotron XRD and DSC

“…The simultaneous collection of thermal and structural data with synchronous pXRD and differential scanning calorimetry (DSC) has been used to assess polymorphic changes of drug molecules with temperature. [14][15][16][17] The use of a synchrotron X-ray source allows for well-defined 2-dimensional X-ray patterns of organic samples to be collected in 1 1C intervals at scan speeds of 10 1C min À1 . Peaks attributed to the aluminium pan can easily be disregarded as they tend to have little overlap with the area of interest for organic crystal structures.…”

Quantum Chemical Study on Mefenamic Acid Polymorphic Forms

“… 23 In addition, the thermal phase transitions of three polymorphic forms as well as their relative stabilities at different temperatures were reported. 24 However, a geometrical characteristic analysis of intermolecular interactions is insufficient in many cases and cannot explain the properties of a solid form that correlate with the anisotropy of a crystal structure.…”