PMID- 26071720
OWN - NLM
STAT- MEDLINE
DCOM- 20160310
LR  - 20150615
IS  - 1089-7690 (Electronic)
IS  - 0021-9606 (Linking)
VI  - 142
IP  - 22
DP  - 2015 Jun 14
TI  - Thermodynamic scaling of molecular dynamics in supercooled liquid state of 
      pharmaceuticals: Itraconazole and ketoconazole.
PG  - 224507
LID - 10.1063/1.4921985 [doi]
AB  - 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 tau(alpha) = 10(-5) s. Furthermore, we plotted the obtained 
      relaxation times as a function of T(-1)v(-gamma), which has revealed that the 
      validity of thermodynamic scaling with the gamma 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.
FAU - Tarnacka, M
AU  - Tarnacka M
AD  - Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 
      Katowice, Poland.
FAU - Madejczyk, O
AU  - Madejczyk O
AD  - Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 
      Katowice, Poland.
FAU - Adrjanowicz, K
AU  - Adrjanowicz K
AD  - NanoBioMedical Centre, ul. Umultowska 85, 61-614 Poznan, Poland.
FAU - Pionteck, J
AU  - Pionteck J
AD  - Leibniz Institute of Polymer Research Dresden, Hohe Strasse 6, D-01069 Dresden, 
      Germany.
FAU - Kaminska, E
AU  - Kaminska E
AD  - 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.
FAU - Kaminski, K
AU  - Kaminski K
AD  - Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 
      Katowice, Poland.
FAU - Paluch, M
AU  - Paluch M
AD  - Institute of Physics, University of Silesia, ul. Uniwersytecka 4, 40-007 
      Katowice, Poland.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Chem Phys
JT  - The Journal of chemical physics
JID - 0375360
RN  - 304NUG5GF4 (Itraconazole)
RN  - R9400W927I (Ketoconazole)
SB  - IM
MH  - Humans
MH  - Itraconazole/*chemistry/therapeutic use
MH  - Ketoconazole/*chemistry/therapeutic use
MH  - Liquid Crystals/chemistry
MH  - Molecular Dynamics Simulation
MH  - *Phase Transition
MH  - *Thermodynamics
MH  - Transition Temperature
EDAT- 2015/06/15 06:00
MHDA- 2016/03/11 06:00
CRDT- 2015/06/15 06:00
PHST- 2015/06/15 06:00 [entrez]
PHST- 2015/06/15 06:00 [pubmed]
PHST- 2016/03/11 06:00 [medline]
AID - 10.1063/1.4921985 [doi]
PST - ppublish
SO  - J Chem Phys. 2015 Jun 14;142(22):224507. doi: 10.1063/1.4921985.