48
K. Adrjanowicz
finding. When controlling exclusively the time scale of the molecular mobility (as
reflected by α-relaxation) or the thermodynamic driving force, this leads to almost the
same crystallization rate of indomethacin in the T-p plane. The very similar behavior
of the crystallization rate along iso-τ α and iso-μ lines indicate that there must
be some hidden link between the kinetic and thermodynamic factors. This explains
why keeping one factor to remain constant upon crystallization progress is immediately sensed by the other one, and why controlling thermodynamics and dynamics
independently eventually leads to the same crystallization rate. Regrettably, it also
demonstrates that with the use of pressure it is impossible to separate thermodynamics
from dynamics. Lastly, by looking at the results presented in Fig. 15 it should be
noted that in the T-p phase space it is also possible to find such iso-invariant points
along which it will be possible to keep under control the crystallization rate (iso-k).
Hence, by ably control of the temperature and pressure conditions, it is possible to
control in a fully aware manner the crystallization behavior of the glass-forming
liquids.
2.5 Crystallization of Single Enantiomers and Racemic
Mixtures on Increased Pressure
Enantiomers are the pair of stereoisomers which are non-superimposable mirror
images of each other. Although they are defined to be the optical isomers with no
difference in the chemical and physical properties, numerous evidences demonstrate
that they can differ in many different features (e.g., flavor or biological activity).
This, potentially, might include also the differences in crystallization tendencies.
Therefore, this study aimed to compare the crystallization tendency of pure enantiomers and their equimolar mixtures at ambient and elevated pressure. The sample
under investigation is a chiral compound, ketoprofen, which belongs to a class of
non-steroidal anti-inflammatory drugs. It is available on the market in the form of a
racemic (1:1) mixture, although its biological activity results only from S-enantiomer
(R is inactive) [76]. The worst scenario is however when one of the enantiomers has
a therapeutic effect, while the other one is toxic (e.g., thalidomide).
Crystallization studies were carried out in the supercooled liquid state of racemic
and enantiopure S-isomer. Both starting materials were completely crystalline with
melting points at around 93.5 and 75 °C, respectively. The idea to compare the crystallization tendency of single enantiomer and the racemic mixture was based on the
isochronal approach, i.e., following crystallization kinetics at various combinations
of (T, p) but approximately the same τ α . Although both materials differ significantly
in the value of the melting temperature, their dynamics in the supercooled liquid state
diverge only slightly [65]. Therefore, to match selected isochrone, log 10 (τ α /s) ∼ = −6,
a slightly different choice of (T, p) points were needed. For racemic ketoprofen this
has included (314 K, 1 MPa), (323 K, 46 MPa), (343 K, 130 MPa), (383 K, 345 MPa)
K. Adrjanowicz
finding. When controlling exclusively the time scale of the molecular mobility (as
reflected by α-relaxation) or the thermodynamic driving force, this leads to almost the
same crystallization rate of indomethacin in the T-p plane. The very similar behavior
of the crystallization rate along iso-τ α and iso-μ lines indicate that there must
be some hidden link between the kinetic and thermodynamic factors. This explains
why keeping one factor to remain constant upon crystallization progress is immediately sensed by the other one, and why controlling thermodynamics and dynamics
independently eventually leads to the same crystallization rate. Regrettably, it also
demonstrates that with the use of pressure it is impossible to separate thermodynamics
from dynamics. Lastly, by looking at the results presented in Fig. 15 it should be
noted that in the T-p phase space it is also possible to find such iso-invariant points
along which it will be possible to keep under control the crystallization rate (iso-k).
Hence, by ably control of the temperature and pressure conditions, it is possible to
control in a fully aware manner the crystallization behavior of the glass-forming
liquids.
2.5 Crystallization of Single Enantiomers and Racemic
Mixtures on Increased Pressure
Enantiomers are the pair of stereoisomers which are non-superimposable mirror
images of each other. Although they are defined to be the optical isomers with no
difference in the chemical and physical properties, numerous evidences demonstrate
that they can differ in many different features (e.g., flavor or biological activity).
This, potentially, might include also the differences in crystallization tendencies.
Therefore, this study aimed to compare the crystallization tendency of pure enantiomers and their equimolar mixtures at ambient and elevated pressure. The sample
under investigation is a chiral compound, ketoprofen, which belongs to a class of
non-steroidal anti-inflammatory drugs. It is available on the market in the form of a
racemic (1:1) mixture, although its biological activity results only from S-enantiomer
(R is inactive) [76]. The worst scenario is however when one of the enantiomers has
a therapeutic effect, while the other one is toxic (e.g., thalidomide).
Crystallization studies were carried out in the supercooled liquid state of racemic
and enantiopure S-isomer. Both starting materials were completely crystalline with
melting points at around 93.5 and 75 °C, respectively. The idea to compare the crystallization tendency of single enantiomer and the racemic mixture was based on the
isochronal approach, i.e., following crystallization kinetics at various combinations
of (T, p) but approximately the same τ α . Although both materials differ significantly
in the value of the melting temperature, their dynamics in the supercooled liquid state
diverge only slightly [65]. Therefore, to match selected isochrone, log 10 (τ α /s) ∼ = −6,
a slightly different choice of (T, p) points were needed. For racemic ketoprofen this
has included (314 K, 1 MPa), (323 K, 46 MPa), (343 K, 130 MPa), (383 K, 345 MPa)