Rapid solid-state analysis of freeze-dried protein formulations using NIR and Raman spectroscopies.
Noninvasive near-infrared (NIR) and Raman spectroscopies were applied to provide a fast and efficient insight into the formation of different mannitol solid forms occurring in freeze-dried formulations. Multivariate data analysis clearly showed the formation of δ-mannitol in the presence of protein, whereas β-mannitol was observed in the absence of protein.The multivariate analysis of the NIR spectra also gave an indication for the formation of mannitol hemihydrate in the absence of protein. Spectroscopic techniques in combination with multivariate analysis can be applied for fast screening and identification of excipient solid-state properties in pharmaceutical formulations.
Department of Pharmaceutics and Analytical Chemistry, Faculty of Pharmaceutical Sciences, University of Copenhagen, 2100 Copenhagen, Denmark. hgr@farma.ku.dk
Holger
H
Grohganz
Delphine
D
Gildemyn
Erik
E
Skibsted
James M
JM
Flink
Jukka
J
Rantanen
D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry*; D005612:Freeze Drying; D019382:Human Growth Hormone / Q000737:chemistry*; D006801:Humans; D007328:Insulin / Q000737:chemistry*; D009682:Magnetic Resonance Spectroscopy; D008353:Mannitol / Q000737:chemistry*; D015394:Molecular Structure; D013059:Spectrum Analysis, Raman; D013678:Technology, Pharmaceutical / Q000379:methods*; D014961:X-Ray Diffraction
D005079:Excipients; D007328:Insulin; D019382:Human Growth Hormone; D008353:Mannitol