Probing The effects of Experimental Conditions on the Character of Drug-Polymer Phase Diagrams Constructed Using Flory-Huggins Theory

Purpose: Amorphous drug-polymer solid dispersions have been found to result in improved drug dissolution rates when compared to their crystalline counterparts. However, when the drug exists in the amorphous form it will possess a higher Gibb’s free energy than its associated crystalline state and can recrystallize. Drug-polymer phase diagrams constructed through the application of the Flory Huggins (F-H) theory contain a wealth of information regarding thermodynamic and kinetic stability of the amorphous drug-polymer system. This study was aimed to evaluate the effects of various experimental conditions on the solubility and miscibility detections of drug-polymer binary system. Methods: Felodipine (FD)-Polyvinylpyrrolidone (PVP) K15 (PVPK15) and FD-Polyvinylpyrrolidone/vinyl acetate (PVP/VA64) were the selected systems for this research. Physical mixtures with different drug loadings were mixed and ball milled. These samples were then processed using Differential Scanning Calorimetry (DSC) and measurements of melting point (Tend) and glass transition (Tg) were detected using heating rates of 0.5, 1.0 and 5.0°C/min. Results: The melting point depression data was then used to calculate the F-H interaction parameter (χ) and extrapolated to lower temperatures to complete the liquid–solid transition curves. The theoretical binodal and spinodal curves were also constructed which were used to identify regions within the phase diagram. The effects of polymer selection, DSC heating rate, time above parent polymer Tg and polymer molecular weight were investigated by identifying amorphous drug miscibility limits at pharmaceutically relevant temperatures. Conclusion: The potential implications of these findings when applied to a non-ambient processing method such as Hot Melt Extrusion (HME) are also discussed.

Kelvin-Helmholtz instability in solar chromospheric jets: theory and observation

Using data obtained by the high-resolution CRisp Imaging SpectroPolarimeter instrument on the Swedish 1 m Solar Telescope, we investigate the dynamics and stability of quiet-Sun chromospheric jets observed at the disk center. Small-scale features, such as rapid redshifted and blueshifted excursions, appearing as high-peed jets in the wings of the Hα line, are characterized by short lifetimes and rapid fading without any descending behavior. To study the theoretical aspects of their stability without considering their formation mechanism, we model chromospheric jets as twisted magnetic flux tubes moving along their axis, and use the ideal linear incompressible magnetohydrodynamic approximation to derive the governing dispersion equation. Analytical solutions of the dispersion equation indicate that this type of jet is unstable to Kelvin–Helmholtz instability (KHI), with a very short (few seconds) instability growth time at high upflow speeds. The generated vortices and unresolved turbulent flows associated with the KHI could be observed as a broadening of chromospheric spectral lines. Analysis of the Hα line profiles shows that the detected structures have enhanced line widths with respect to the background. We also investigate the stability of a larger-scale Hα jet that was ejected along the line of sight. Vortex-like features, rapidly developing around the jet’s boundary, are considered as evidence of the KHI. The analysis of the energy equation in the partially ionized plasma shows that ion–neutral collisions may lead to fast heating of the KH vortices over timescales comparable to the lifetime of chromospheric jets.