Influence of High Pressure on the Local Order and Dynamical Properties of the Selected Azole Antifungals

Abstract

Dielectric studies under various temperature (T) and pressure (p) conditions on five active pharmaceutical ingredients (APIs) with antifungal propertiesitraconazole (ITZ), posaconazole (POS), terconazole (TER), ketoconazole (KET), and fluconazole (FLU)were carried out. We have thoroughly studied the connection between the pressure coefficient of the glass transition temperature (dT g /dp) and the activation volume of both relaxation modes (ΔV α , ΔV δ/α′ ) with respect to the molecular weight (M w ) or molar volume (V m ) in these systems. Besides, high pressure data revealed that the time scale separation between αand δor α′-processes increases with pressure in ITZ and TER. What is more, the activation entropy, which is a measure of cooperativity, calculated from the Eyring model for the secondary (β)-relaxation in ITZ and POS, increased and decreased, respectively, in the compressed samples. To understand these peculiar results, we have carried out X-ray diffraction (XRD) measurements on the pressure-densified glasses and found that pressure may induce frustration in molecular organization and destroy the medium-range order while enhancing the short-range correlations between molecules. This finding allowed us to conclude that varying molecular spatial arrangement is responsible for the extraordinary dynamical behavior of ITZ, POS, and TER at high pressure.

The Influence of PVP Polymer Topology on the Liquid Crystalline Order of Itraconazole in Binary Systems

“…More precisely, the thermal event at 348 K corresponds to the transition of API from the smectic (Sm) to nematic (N) phase ( T Sm‑N ), while that at 364 K is related to a transition from the N to isotropic (I) phase ( T N‑I ). Herein, it is worth noting that the obtained thermogram of neat ITZ and the determined phase transitions are in good agreement with the data reported in previous works. ,,− , …”

“…Herein, it is worth noting that the obtained thermogram of neat ITZ and the determined phase transitions are in good agreement with the data reported in previous works. 16,24,[26][27][28][29][30][31][32][33]35 Next, we registered thermograms of ITZ−PVP 95:5 w/w ASDs. As can be observed in Figure 2, regardless of the type of polymer applied in the binary system, the T g remains unchanged with respect to neat API, while the temperatures of both LC transitions shift toward lower values of T: to 339 K (T Sm-N ) and 359 K (T N-I ).…”

“…Further studies on the molecular dynamics of ITZ carried out by Tarnacka et al clearly indicated that the observed endothermic events are indeed associated with the formation of the nematic N (363 K) and smectic Sm (346 K) phases. Since that time, ITZ has been thoroughly studied by different research groups. − Furthermore, new reports still continue to emerge, shedding light on their remarkably intriguing LC properties and the possibilities for their modification. Herein, one can mention a paper by Teerekapibal et al, who investigated the influence of the cooling rate (ϕ) of liquid ITZ on the occurrence of mesophases .…”

The impact of H/D exchange on the thermal and structural properties as well as high-pressure relaxation dynamics of melatonin

“…Herein, it is worth reminding that for typical but strongly H-bonded systems, such as polyalcohols, rather lower dT g /dp (< 70 K/GPa) 54 , and ΔV α at T g (< 40 cm 3 /mol) 55 have been obtained. However, it should be mentioned that similar, in comparison to MLT, values of the first parameter, i.e., dT g /dp coefficient, have been reported for several weakly H-bonded active substances, e.g., fluconazole (183 K/GPa) 56 , ibuprofen (195 K/GPa) 57 , salol (204 K/GPa) 58 , or curcumin (197 K/GPa) 59 . Note that also in Refs.…”

“…Note that also in Refs. 56 , 58 , a slightly greater or lower Δ V α with respect to MLT has been given for fluconazole and salol (Δ V α = 296 and 170 cm 3 /mol, respectively). The difference in the pressure coefficient of the glass transition temperature, and especially activation volume at the T g for both compounds, clearly show that the dynamics of HBs in the native and partially-deuterated MLT is different and influences the structural relaxation.…”