PT  - JOURNAL ARTICLE
AU  - Romero-Torres, Saly
AU  - Wikström, Håkan
AU  - Grant, Edward R.
AU  - Taylor, Lynne S.
TI  - Monitoring of Mannitol Phase Behavior during Freeze-Drying Using Non-Invasive Raman Spectroscopy
DP  - 2007 Mar 01
TA  - PDA Journal of Pharmaceutical Science and Technology
PG  - 131--145
VI  - 61
IP  - 2
4099  - http://journal.pda.org/content/61/2/131.short
4100  - http://journal.pda.org/content/61/2/131.full
SO  - PDA J Pharm Sci Technol2007 Mar 01; 61
AB  - In this study, the feasibility of using Raman spectroscopy as a fast, non-invasive, non-destructive technique to monitor crystallization and polymorphic transformations during freeze-drying is assessed using mannitol as the model compound. In-line process monitoring was achieved by interfacing a Raman spectrometer with a fiber-optically coupled, long-working-distance probe to a freeze-drier. By analyzing the process data using principal component analysis, it was possible to extract valuable information pertaining to ice and mannitol crystallization points, the polymorphic form of mannitol, and dehydration of the mannitol hydrate. In conclusion, Raman spectroscopy is a potentially useful technique to monitor physical changes during freeze-drying.