skip to main content

Title: Thermodynamic scaling of molecular dynamics in supercooled liquid state of pharmaceuticals: Itraconazole and ketoconazole

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{sub 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{sub 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 {sub α} = 10{sup −5} s. Furthermore, we plotted the obtained relaxation times as a function of T{sup −1}v{sup −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 withinmore » 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.« less
Authors:
; ; ;  [1] ;  [2] ;  [3] ;  [4] ;  [5]
  1. Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 Katowice (Poland)
  2. (Poland)
  3. NanoBioMedical Centre, ul. Umultowska 85, 61-614 Poznan (Poland)
  4. Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, D-01069 Dresden (Germany)
  5. 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)
Publication Date:
OSTI Identifier:
22415976
Resource Type:
Journal Article
Resource Relation:
Journal Name: Journal of Chemical Physics; Journal Volume: 142; Journal Issue: 22; Other Information: (c) 2015 AIP Publishing LLC; Country of input: International Atomic Energy Agency (IAEA)
Country of Publication:
United States
Language:
English
Subject:
37 INORGANIC, ORGANIC, PHYSICAL AND ANALYTICAL CHEMISTRY; AZOLES; DIELECTRIC MATERIALS; DRUGS; GLASS; KETONES; LIQUIDS; MOLECULAR DYNAMICS METHOD; MOLECULES; PHASE TRANSFORMATIONS; PRESSURE COEFFICIENT; PRESSURE RANGE GIGA PA; RELAXATION TIME; SPECTROSCOPY; TRANSITION TEMPERATURE