Crystallization of Amorphous Pharmaceuticals at Ambient and Elevated …
63
a
b
Fig. 3 Comparisons of temperature dependences of normalized dielectric strengths N of four
selected pharmaceuticals FLU (red triangles), NIM (orange diamonds), EZB (green squares) and
PBC (blue circles). a Data as a function of temperature (T ) and b as a function of T g + T
2.2 Isothermal Crystallization Studies
Besides the non-isothermal studies, the crystallization of amorphous APIs can be
monitored by BDS also at isothermal conditions. During such experiments the spectra
of complex dielectric permittivity (ε*(ω) = ε
(ω) – iε
(ω)) of the examined pharmaceutical are registered at a chosen temperature, in the supercooled liquid region, at
the specified time intervals until the sample fully re-crystallize. Figure 4 shows the
representative results from discussed measurements i.e. frequency dependencies of
the real and the imaginary part of the complex dielectric permittivity of NIM panels
a and b, respectively. During this experiment NIM was stored at T = 328 K, while
the set time interwall was equal to 120 s. The total re-crystallization of the sample
occurred after approximately 90 min.
It is clearly seen that after an induction time, during which no changes between
the spectra were observed, both the amplitude of α-relaxation loss peak as well as
a static dielectric permittivity begin to rapidly decrease with time. As it has been
already mentioned, such a sudden drop in the α is typical for the re-crystallization
process during which a reduction in the number of reorienting dipoles, contributing
to the structural relaxation, proceeds.
To properly analyse the kinetics of devitrification of amorphous pharmaceuticals,
data corresponding to the real permittivity should be normalized (ε
N ) as follows:
63
a
b
Fig. 3 Comparisons of temperature dependences of normalized dielectric strengths N of four
selected pharmaceuticals FLU (red triangles), NIM (orange diamonds), EZB (green squares) and
PBC (blue circles). a Data as a function of temperature (T ) and b as a function of T g + T
2.2 Isothermal Crystallization Studies
Besides the non-isothermal studies, the crystallization of amorphous APIs can be
monitored by BDS also at isothermal conditions. During such experiments the spectra
of complex dielectric permittivity (ε*(ω) = ε
(ω) – iε
(ω)) of the examined pharmaceutical are registered at a chosen temperature, in the supercooled liquid region, at
the specified time intervals until the sample fully re-crystallize. Figure 4 shows the
representative results from discussed measurements i.e. frequency dependencies of
the real and the imaginary part of the complex dielectric permittivity of NIM panels
a and b, respectively. During this experiment NIM was stored at T = 328 K, while
the set time interwall was equal to 120 s. The total re-crystallization of the sample
occurred after approximately 90 min.
It is clearly seen that after an induction time, during which no changes between
the spectra were observed, both the amplitude of α-relaxation loss peak as well as
a static dielectric permittivity begin to rapidly decrease with time. As it has been
already mentioned, such a sudden drop in the α is typical for the re-crystallization
process during which a reduction in the number of reorienting dipoles, contributing
to the structural relaxation, proceeds.
To properly analyse the kinetics of devitrification of amorphous pharmaceuticals,
data corresponding to the real permittivity should be normalized (ε
N ) as follows: