Monitoring of Pentoxifylline Thermal Behavior by Novel Simultaneous Laboratory Small and Wide X-Ray Scattering (SWAXS) and Differential Scanning Calorimetry (DSC)

<div><p>The thermal and structural evolutions associated to active pharmaceutical ingredient (API) purity are monitored using a laboratory instrument (S3-MicroCaliX) allowing simultaneous time-resolved X-ray scattering at both wide and small angles (SWAXS) as a function of temperature. This is performed simultaneously with differential scanning calorimetric (DSC) that is carried out in the same apparatus at scanning rate of 2 K/min on the same sample in the range from 20° to 200°C. We have studied simultaneous thermal and structural properties of pentoxifylline, as an active pharmaceutical ingredient (API), for its purity quality control. We have found a satisfying API purity, due to obtained melting temperature and enthalpy values, which are in a well agreement with literature. We have also found that the combination of these techniques allows the thermal monitoring of scanning rates of 2 K/min, continuously without the need for static thermal equilibration, particularly for X-ray spectra. Hence, DSC and SWAXS allowing better identification of the structural thermal events recorded by following of the phase transitions simultaneously. This interpretation is much better possible when X-ray scattering at small and wide angles is coupled with DSC from the same sample. Hence, as a laboratory tool, the method presents a reproducible thermal and crystallographic API purity quality control of non-complex samples, as crucial information for pharmaceutical technology.</p></div

DSC spectra of pentoxifylline: Heating scan with a base line subtraction and slope correction displaying melting transition.

<p>Cooling scan with a base line subtraction displays a stabile amorphous state.</p

SWAXS cooling scans spectra of pentoxifylline in the temperature range of 140 to 80°C: a) SAXS cooling scan, b) WAXS cooling scan in the three dimensional plot.

<p>SWAXS cooling scans spectra of pentoxifylline in the temperature range of 140 to 80°C: a) SAXS cooling scan, b) WAXS cooling scan in the three dimensional plot.</p

a) WAXS heating scan in the three-dimensional plot, b) WAXS heating scans in a two dimensional contour plot.

<p>(SAXS exposure time one minute per frame, which corresponds to two°C per frame).</p

Sketch of the experimental setup.

<p>The experimental arrangement for time-resolved X-ray measurements at the Austrian SAXS–beamline at the ELETTRA synchrotron light source is shown. For T-jump experiments, an erbium laser beam (IR), wavelength λ = 1.5 µm, was directed via a prism onto the sample capillary which was thermostated with a Peltier unit. Laser pulse energy was 2 J within 2 ms resulting in an average T-jump amplitude of 10–12°C. The exposure time was 10 ms per frame. For T-drop experiments, the empty X-ray capillary was pre-cooled in a stream of nitrogen adjusted to −20°C. LDL samples, preheated to approx.10°C above the melting transition, were injected by a motor-driven syringe. A drop in temperature of about 20°C could be induced in about 3–4 s. The exposure time was 250 ms per frame.</p

Time-resolved nanophase transition in LDL.

<p>The rise in the integrated intensity of the 1st side-maximum upon laser jump is shown as a function of time (A). The time slicing was 10 ms per image. The time point of laser flash is set to zero seconds. The error function of statistical variation displays a maximum inaccuracy in time of about 5 ms. Thus, the offset in transition is much shorter than the sampling time of 10 ms and the 2 ms of laser flash. The integrated intensities of the 1st side-maximum obtained by static measurements within a temperature range of 0°C and 50°C with a step width of 5°C (B, left panel) are correlated to the time-course of integrated intensities of the 1st side-maximum obtained by dynamic measurements (B, right panel). For static measurements, a measuring time of 30 s and an equilibration time of 10 minutes at each temperature was chosen. For dynamic measurements, the measuring time per frame was 250 ms. A half-time of 2 seconds, corresponding to a temperature drop of about 10°C, could be achieved to pass through the transition temperature. The decline in integrated intensity strictly followed the drop in temperature. Tm for the LDL sample shown was about 22°C, as determined by microcalorimetry.</p

Long-Chain Li and Na Alkyl Carbonates as Solid Electrolyte Interphase Components: Structure, Ion Transport, and Mechanical Properties

The solid electrolyte interphase (SEI) in Li and Na ion batteries forms when highly reducing or oxidizing electrode materials come into contact with a liquid organic electrolyte. Its ability to form a mechanically robust, ion-conducting, and electron-insulating layer critically determines performance, cycle life, and safety. Li or Na alkyl carbonates (LiAC and NaAC, respectively) are lead SEI components in state-of-the-art carbonate based electrolytes, and our fundamental understanding of their charge transport and mechanical properties may hold the key to designing electrolytes forming an improved SEI. We synthesized a homologous series of LiACs and NaACs from methyl to octyl analogues and characterized them with respect to structure, ionic conductivity, and stiffness. The compounds assume layered structures except for the lithium methyl carbonate. Room-temperature conductivities were found to be ∼10^–9 S cm^–1 for lithium methyl carbonate, <10^–12 S cm^–1 for the other LiACs, and <10^–12 S cm^–1 for the NaACs with ion transport mostly attributed to grain boundaries. While LiACs show stiffnesses of ∼1 GPa, NaACs become significantly softer with increasing chain lengths. These findings will help to more precisely interpret the complex results from charge transport and mechanical characterization of real SEIs and can give a rationale for influencing the SEI’s mechanical properties via the electrolyte