In this paper, broadband dielectric
spectroscopy (BDS) has been
applied to study the molecular dynamics and crystallization kinetics
of the antihyperlipidemic active pharmaceutical ingredient (API),
gemfibrozil (GEM), as well as its deuterated (dGEM) and methylated
(metGEM) derivatives, characterized by different types and strengths
of intermolecular interactions. Moreover, calorimetric and infrared
measurements have been carried out to characterize the thermal properties
of examined samples and to probe a change in the H-bonding pattern
in GEM, respectively. We found that the dielectric spectra of all
examined compounds, collected below the glass transition temperature
(
T
g
), reveal the presence of two secondary
relaxations (β, γ). According to the coupling model (CM)
predictions, it was assumed that the slower process (β) is of
JG type, whereas the faster one (γ) has an intramolecular origin.
Interestingly, the extensive crystallization kinetics measurements
performed after applying two paths, i.e., the standard procedure (cooling
and subsequently heating up to the appropriate temperature,
T
c
), as well as annealing at two temperatures
in the vicinity of
T
g
and further heating
up to
T
c
, showed that the annealing increases
the crystallization rate in the case of native API, while the thermal
history of the sample has no significant impact on the pace of this
process in the two derivatives of GEM. Analysis of the dielectric
strength (Δε) of the α-process during annealing,
together with the results of Fourier transform infrared spectroscopy
(FTIR) measurements, suggested that the reorganization within dimeric
structures formed between the GEM molecules is responsible for the
observed behavior. Importantly, our results differ from those obtained
by Tominaka et al. (
Physical Stabilization of Pharmaceutical
Glasses Based on Hydrogen Bond Reorganization under Sub-T
g
Temperature
Tominaka
S.
Kawakami
K.
Fukushima
M.
Miyazaki
A.
Tominaka
S.
Kawakami
K.
Fukushima
M.
Miyazaki
A.
10.1021/acs.molpharmaceut.6b00866
28043129
Mol. Pharm.
2017
14
264
273
), who demonstrated that the sub-
T
g
annealing of ritonavir (RTV), which is able to form extensive
supramolecular hydrogen bonds, protects this active substance against
crystallization. Therefore, based on these contradictory reports,
one can hypothesize that materials forming H-bonded structures, characterized
by varying architecture, may behave differen...