May 2009
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better chemical stability of the drug in IF. This shows that
utilization of suitable amorphous materials as excipients
could be a promising approach to stabilizing lyophilized for-
mulations of moisture-sensitive drugs. It should be noted,
however, that such amorphous materials might carry a risk of
causing crystallization by water absorption as exhibited in
this study. Therefore when such amorphous excipients are
used for lyophilized formulations, it is crucial to evaluate the
amount of water which formulations can hold without risk of
crystallization. It is also important to protect the formula-
tions from moisture as much as possible and to monitor
2
Fig. 9. H-NMR Spectra of D O in IF in the Presence of 2% Water (A)
2
and 8% Water (B) at 40 °C
water content adequately during the manufacturing process
2
though signal was not detected from IF at 20 °C in the pres- and storage. This study also indicated that H-NMR analysis
ence of a low water content (2%) due to insufficient peak in- of water mobility is a useful tool for investigating the chemi-
tensity, a broad single peak was observed by increasing tem- cal and physical stability of drugs in formulations.
perature up to 40 °C, indicating that only associated water
Acknowledgements The authors would like to thank Mr. Masao Nagao
for assistance with the preparation of the lyophilized formulations and Toray
Research Center for performing the NMR measurement and for helpful dis-
existed in the formulation (Fig. 9). Because the signal of re-
stricted water in IF was broader than that in MF at each tem-
perature, it was suggested that IF had a water population with cussion.
a lower mobility than that of MF due to the higher water
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