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Mass Spectrometric Approaches to Study Protein Structure and Interactions in Lyophilized Powders
Published on: April 14, 2015
Characterization of mannitol polymorphic forms in lyophilized protein formulations using a multivariate curve
Yong Xie1, Wenjin Cao, Sampathkumar Krishnan
1Pharmaceutics Department, Amgen Inc., One Amgen Center Dr., Thousand Oaks, California 91320, USA. yongx@amgen.com
Pharmaceutical Research
|June 5, 2008
Summary
A new Raman spectroscopy method using multivariate curve resolution (MCR) accurately quantifies five mannitol solid-state forms in lyophilized protein products. This technique aids in monitoring and improving drug product quality.
Area of Science:
- Pharmaceutical Sciences
- Analytical Chemistry
- Spectroscopy
Background:
- Mannitol is a crucial excipient in lyophilized protein formulations, and its solid-state forms can impact drug product stability and efficacy.
- Controlling and characterizing mannitol's polymorphic forms are essential for ensuring consistent drug product quality.
Purpose of the Study:
- To develop a novel multivariate curve resolution (MCR)-based Raman spectroscopic method.
- To characterize and quantify five known mannitol solid-state forms in lyophilized protein formulations.
Main Methods:
- Developed a multivariate quantitation method using second derivative Raman spectra of five mannitol forms (three anhydrous crystalline, one hemihydrate, one amorphous).
- Validated the method using binary mixtures and prediction residue analysis, with a 5% quantitation limit.
- Utilized X-ray powder diffractometry for confirmation of mannitol forms.
Main Results:
- Successfully characterized and quantified various mannitol polymorphic forms using Raman spectra.
- Results were consistent with X-ray powder diffraction data.
- Demonstrated the method's applicability for monitoring and controlling mannitol polymorphic forms in lyophilized drug products.
Conclusions:
- Developed an MCR-Raman method for quantitative determination of five mannitol polymorphic forms.
- The method is effective in the presence of sucrose and protein.
- This technique has implications for monitoring and enhancing drug product quality during formulation and process development.
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