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Microscale freeze-drying with Raman spectroscopy as a tool for process development
- Source :
- Kauppinen, A, Toiviainen, M, Aaltonen, J, Korhonen, O, Järvinen, K, Juuti, M, Pellinen, R & Ketolainen, J 2013, ' Microscale freeze-drying with Raman spectroscopy as a tool for process development ', Analytical Chemistry, vol. 85, no. 4, pp. 2109-2116 . https://doi.org/10.1021/ac3027349
- Publication Year :
- 2013
-
Abstract
- Until recently, the freeze-drying process and formulation development have suffered from a lack of microscale analytical tools. Using such an analytical tool should decrease the required sample volume and also shorten the duration of the experiment compared to a laboratory scale setup. This study evaluated the applicability of Raman spectroscopy for in-line monitoring of a microscale freeze-drying process. The effect of cooling rate and annealing step on the solid-state formation of mannitol was studied. Raman spectra were subjected to principal component analysis to gain a qualitative understanding of the process behavior. In addition, mannitol solid-state form ratios were semiquantitatively analyzed during the process with a classical least-squares regression. A standard cooling rate of 1 °C/min with or without an annealing step at −10 °C resulted in a mixture of α, β, δ, and amorphous forms of mannitol. However, a standard cooling rate induced the formation of mannitol hemihydrate, and a secondary drying temperature of +60 °C was required to transform the hemihydrate form to the more stable anhydrous polymorphs. A fast cooling rate of 10 °C/min mainly produced δ and amorphous forms of mannitol, regardless of annealing. These results are consistent with those from larger scale equipment. In-line monitoring the solid-state form of a sample is feasible with a Raman spectrometer coupled microscale freeze-drying stage. These results demonstrate the utility of a rapid, in-line, low sample volume method for the semiquantitative analysis of the process and formulation development of freeze-dried products on the microscale.
- Subjects :
- Annealing (metallurgy)
Analytical chemistry
02 engineering and technology
Spectrum Analysis, Raman
030226 pharmacology & pharmacy
Analytical Chemistry
law.invention
03 medical and health sciences
Freeze-drying
symbols.namesake
0302 clinical medicine
law
medicine
Mannitol
Crystallization
Least-Squares Analysis
Microscale chemistry
Principal Component Analysis
Calorimetry, Differential Scanning
Chemistry
Near-infrared spectroscopy
Temperature
021001 nanoscience & nanotechnology
Amorphous solid
Freeze Drying
symbols
0210 nano-technology
Raman spectroscopy
medicine.drug
Subjects
Details
- Language :
- English
- Database :
- OpenAIRE
- Journal :
- Kauppinen, A, Toiviainen, M, Aaltonen, J, Korhonen, O, Järvinen, K, Juuti, M, Pellinen, R & Ketolainen, J 2013, ' Microscale freeze-drying with Raman spectroscopy as a tool for process development ', Analytical Chemistry, vol. 85, no. 4, pp. 2109-2116 . https://doi.org/10.1021/ac3027349
- Accession number :
- edsair.doi.dedup.....aad15a084dd5e6b30353b011fdcbc30b