106
K. Kawakami
6.6 Impact of Moisture Sorption on Crystallization
Crystallization is frequently accelerated by moisture sorption, because the solvent
can act as a plasticizer. The degree of acceleration may be explained by the decrease
in T g . Figure 6.11a shows that T g of freeze-dried ritonavir glass was lowered by
storage under humid atmosphere [11]. Figure 6.11b illustrates the t 10 of the ritonavir
glass stored under both dry and humid conditions. As discussed earlier, quenched
ritonavir glass was more stable than that expected from the universal line. However,
t 10 of the freeze-dried glass could be found on the universal line, most likely because
the crystallization was enhanced by an increase in the surface area. The t 10 for the
ritonavir glass stored under humid condition was also found on the universal line,
indicating that T g /T can be regarded as a controlling parameter even for the glass
with the plasticizer.
The impact of moisture sorption is sometimes more significant than that anticipated from change in T g . Figure 6.1 shows the physical stability data of nifedipine
glass acquired after careful experimentation. In this experiment, crystalline powder
of nifedipine was dried in a vacuum oven at 50 °C and stored in a desiccator with
silica gel prior to usage. Then, the dried powder was loaded into a hermetically sealed
pan under a dried nitrogen atmosphere and subjected to the melt-quench process in
DSC. All these steps have a significant impact on the stability of the nifedipine glass,
although changes in the moisture levels during these treatments are insignificant. In
this case, the bulk T g does not work for the prediction of the physical stability, rather
the T g of the surface molecules appears to be more important.
Fig. 6.11 a Effect of storage relative humidity (RH) on T g (onset values) of the freeze-dried
ritonavir glass. T g of the quenched glass is also presented. b t 10 of Ritonavir glass as a function of
T g /T. () quenched glass, (●) freeze-dried glass stored under dry condition, (◯) Freeze-dried glass
stored under humid condition. The storage temperature and humidity for the freeze-dried glasses
are indicated in the Figure. Figures are adopted with modification form Ref. [11] with permission
of Elsevier
K. Kawakami
6.6 Impact of Moisture Sorption on Crystallization
Crystallization is frequently accelerated by moisture sorption, because the solvent
can act as a plasticizer. The degree of acceleration may be explained by the decrease
in T g . Figure 6.11a shows that T g of freeze-dried ritonavir glass was lowered by
storage under humid atmosphere [11]. Figure 6.11b illustrates the t 10 of the ritonavir
glass stored under both dry and humid conditions. As discussed earlier, quenched
ritonavir glass was more stable than that expected from the universal line. However,
t 10 of the freeze-dried glass could be found on the universal line, most likely because
the crystallization was enhanced by an increase in the surface area. The t 10 for the
ritonavir glass stored under humid condition was also found on the universal line,
indicating that T g /T can be regarded as a controlling parameter even for the glass
with the plasticizer.
The impact of moisture sorption is sometimes more significant than that anticipated from change in T g . Figure 6.1 shows the physical stability data of nifedipine
glass acquired after careful experimentation. In this experiment, crystalline powder
of nifedipine was dried in a vacuum oven at 50 °C and stored in a desiccator with
silica gel prior to usage. Then, the dried powder was loaded into a hermetically sealed
pan under a dried nitrogen atmosphere and subjected to the melt-quench process in
DSC. All these steps have a significant impact on the stability of the nifedipine glass,
although changes in the moisture levels during these treatments are insignificant. In
this case, the bulk T g does not work for the prediction of the physical stability, rather
the T g of the surface molecules appears to be more important.
Fig. 6.11 a Effect of storage relative humidity (RH) on T g (onset values) of the freeze-dried
ritonavir glass. T g of the quenched glass is also presented. b t 10 of Ritonavir glass as a function of
T g /T. () quenched glass, (●) freeze-dried glass stored under dry condition, (◯) Freeze-dried glass
stored under humid condition. The storage temperature and humidity for the freeze-dried glasses
are indicated in the Figure. Figures are adopted with modification form Ref. [11] with permission
of Elsevier