74
J. Knapik-Kowalczuk et al.
Fig. 13 a Long-term isothermal XRD measurement of PBC carried out at T = 298 K and p =
0.1 MPa; b dielectric spectra of the real part of the complex dielectric permittivity of PBC during
isothermal dielectric experiment performed at T = 333 K and p = 0.1 MPa; c dielectric spectra of
the real part of the complex dielectric permittivity of PBC during isothermal dielectric experiment
performed at T = 333 K and p = 10 MPa.
Since the pressure is not applied throughout the whole manufacturing process,
it has been proposed, to use BDS as a method monitoring drugs physical stability
at imitating this short-time compression exposure conditions. By employing dielectric spectroscopy with a high-pressure setup, it is possible to quickly compress and
decompress the sample at defined by the user temperature conditions. The available
by this equipment pressure range starts from 0.1 MPa and going up to 1.8 GPa, what
far exceeds the pharmacists’ needs. It is because the usually used compression during
the tabletting process ranges from 50 to 250 MPa, while pressures not higher than
20 MPa can be exerted on the sample during HME. It is also worth noting that by
applying the high-pressure dielectric setup it is possible to monitor physical stability
of amorphous drugs during all, imitating production steps (i.e. compression, decompression, storage time, second compression, temperature change). This option allows
to assess in which particular part of production line the API is exposed to the most
danger for stability conditions. In Fig. 14, the comparison of results obtained for PBC
stored at: (i) ambient pressure; (ii) elevated pressure; and (iii) ambient pressure after
the compression and decompression procedure are presented. It can be well seen
that the elevated pressure triggers PBC’s re-crystallization. Thus, even the slightest
pressure exerted to the sample promotes the formation of crystallization nuclei, and
consequently even after decompression PBC’s crystal growth might be observed.
J. Knapik-Kowalczuk et al.
Fig. 13 a Long-term isothermal XRD measurement of PBC carried out at T = 298 K and p =
0.1 MPa; b dielectric spectra of the real part of the complex dielectric permittivity of PBC during
isothermal dielectric experiment performed at T = 333 K and p = 0.1 MPa; c dielectric spectra of
the real part of the complex dielectric permittivity of PBC during isothermal dielectric experiment
performed at T = 333 K and p = 10 MPa.
Since the pressure is not applied throughout the whole manufacturing process,
it has been proposed, to use BDS as a method monitoring drugs physical stability
at imitating this short-time compression exposure conditions. By employing dielectric spectroscopy with a high-pressure setup, it is possible to quickly compress and
decompress the sample at defined by the user temperature conditions. The available
by this equipment pressure range starts from 0.1 MPa and going up to 1.8 GPa, what
far exceeds the pharmacists’ needs. It is because the usually used compression during
the tabletting process ranges from 50 to 250 MPa, while pressures not higher than
20 MPa can be exerted on the sample during HME. It is also worth noting that by
applying the high-pressure dielectric setup it is possible to monitor physical stability
of amorphous drugs during all, imitating production steps (i.e. compression, decompression, storage time, second compression, temperature change). This option allows
to assess in which particular part of production line the API is exposed to the most
danger for stability conditions. In Fig. 14, the comparison of results obtained for PBC
stored at: (i) ambient pressure; (ii) elevated pressure; and (iii) ambient pressure after
the compression and decompression procedure are presented. It can be well seen
that the elevated pressure triggers PBC’s re-crystallization. Thus, even the slightest
pressure exerted to the sample promotes the formation of crystallization nuclei, and
consequently even after decompression PBC’s crystal growth might be observed.