title: Thermodynamic scaling of molecular dynamics in supercooled liquid state of pharmaceuticals: Itraconazole and ketoconazole.
abstract: Pressure-Volume-Temperature (PVT) measurements and broadband dielectric spectroscopy were carried out to investigate molecular dynamics and to test the validity of thermodynamic scaling of two homologous compounds of pharmaceutical activity: itraconazole and ketoconazole in the wide range of thermodynamic conditions. The pressure coefficients of the glass transition temperature (dT(g)/dp) for itraconazole and ketoconazole were determined to be equal to 183 and 228 K/GPa, respectively. However, for itraconazole, the additional transition to the nematic phase was observed and characterized by the pressure coefficient dT(n)/dp = 258 K/GPa. From PVT and dielectric data, we obtained that the liquid-nematic phase transition is governed by the relaxation time since it occurred at constant τ(α) = 10(-5) s. Furthermore, we plotted the obtained relaxation times as a function of T(-1)v(-γ), which has revealed that the validity of thermodynamic scaling with the γ exponent equals to 3.69 ± 0.04 and 3.64 ± 0.03 for itraconazole and ketoconazole, respectively. Further analysis of the scaling parameter in itraconazole revealed that it unexpectedly decreases with increasing relaxation time, which resulted in dramatic change of the shape of the thermodynamic scaling master curve. While in the case of ketoconazole, it remained the same within entire range of data (within experimental uncertainty). We suppose that in case of itraconazole, this peculiar behavior is related to the liquid crystals' properties of itraconazole molecule.
authors.affiliation: Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Tarnacka
authors.affiliation: Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.
authors.forename: O
authors.initials: O
authors.lastname: Madejczyk
authors.affiliation: NanoBioMedical Centre, ul. Umultowska 85, 61-614 Poznan, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Adrjanowicz
authors.affiliation: Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, D-01069 Dresden, Germany.
authors.forename: J
authors.initials: J
authors.lastname: Pionteck
authors.affiliation: Department of Pharmacognosy and Phytochemistry, School of Pharmacy and Division of Laboratory Medicine in Sosnowiec, Medical University of Silesia, ul. Jagiellonska 4, 41-200 Sosnowiec, Poland.
authors.forename: E
authors.initials: E
authors.lastname: Kaminska
authors.affiliation: Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.
authors.forename: K
authors.initials: K
authors.lastname: Kamiński
authors.affiliation: Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice, Poland.
authors.forename: M
authors.initials: M
authors.lastname: Paluch
mesh_terms: D006801:Humans; D017964:Itraconazole / Q000737:chemistry* / Q000627:therapeutic use; D007654:Ketoconazole / Q000737:chemistry* / Q000627:therapeutic use; D050866:Liquid Crystals / Q000737:chemistry; D056004:Molecular Dynamics Simulation; D044367:Phase Transition; D013816:Thermodynamics; D044366:Transition Temperature
chemical_list: D017964:Itraconazole; D007654:Ketoconazole