Application of Optical Coherence Tomography Freeze-Drying Microscopy for Designing Lyophilization Process and Its Impact on Process Efficiency and Product Quality
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Optical coherence tomography freeze-drying microscopy (OCT-FDM) is a novel technique that allows the three-dimensional imaging of a drug product during the entire lyophilization process. OCT-FDM consists of a single-vial freeze dryer (SVFD) affixed with an optical coherence tomography (OCT) imaging system. Unlike the conventional techniques, such as modulated differential scanning calorimetry (mDSC) and light transmission freeze-drying microscopy, used for predicting the product collapse temperature (Tc), the OCT-FDM approach seeks to mimic the actual product and process conditions during the lyophilization process. However, there is limited understanding on the application of this emerging technique to the design of the lyophilization process. In this study, we investigated the suitability of OCT-FDM technique in designing a lyophilization process. Moreover, we compared the product quality attributes of the resulting lyophilized product manufactured using Tc, a critical process control parameter, as determined by OCT-FDM versus as estimated by mDSC. OCT-FDM analysis revealed the absence of collapse even for the low protein concentration (5 mg/ml) and low solid content formulation (1%w/v) studied. This was confirmed by lab scale lyophilization. In addition, lyophilization cycles designed using Tc values obtained from OCT-FDM were more efficient with higher sublimation rate and mass flux than the conventional cycles, since drying was conducted at higher shelf temperature. Finally, the quality attributes of the products lyophilized using Tc determined by OCT-FDM and mDSC were similar, and product shrinkage and cracks were observed in all the batches of freeze-dried products irrespective of the technique employed in predicting Tc.
KEY WORDSlyophilization optical coherence freeze-drying microscopy collapse temperature glass transition temperature protein formulation
The authors would like to thank Dr. Haiou Qu and Dr. Yifan Wang, ORISE Fellows at the Food and Drug Administration, for their contribution.
Compliance with Ethical Standards
The opinions expressed in this work are only of the author and should not be construed to represent FDA’s views or policies.
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- 1.LaTorre-Snyder M. Lyophilization: The basics. Pharmaceutical Processing. 2017. www.pharmpro.com/article/2017/3/lyophilization-basics.
- 11.MacKenzie AP. Collapse during freeze drying—qualitative and quantitative aspects. In: Goldblith SA, Rey L, Rothmayr WW, editors. Freeze Drying and Advanced Food Technology. London: Academic Press. 1975. P. 277–307.Google Scholar
- 12.Pikal MJ. Use of laboratory data in freeze drying process design: heat and mass transfer coefficients and the computer simulation of freeze drying. J Parenter Sci Technol Publ Parenter Drug Assoc. 1985;39(3):115–39.Google Scholar
- 16.Johnson RLL. Freeze-drying protein formulations above their collapse temperatures: possible issues and concerns. Am Pharm Rev. 2011;14(3):50–4.Google Scholar
- 18.Greco K, Mujat M, Galbally-Kinney KL, Hammer DX, Ferguson RD, Iftimia N, et al. Accurate prediction of collapse temperature using optical coherence tomography-based freeze-drying microscopy. J Pharm Sci. 2013;102(6):1773–85.Google Scholar
- 19.Mujat M, Greco K, Galbally-Kinney KL, Hammer DX, Ferguson RD, Iftimia N, et al. Optical coherence tomography-based freeze-drying microscopy. Biomed Opt Express. 2012;3(1):55–63.Google Scholar
- 28.Searles J. Observation and implications of sonic water vapor flow during freeze-drying. Am Pharm Rev. 2004;7:58–69.Google Scholar
- 30.Schersch K, Betz O, Garidel P, Muehlau S, Bassarab S, Winter G. Systematic investigation of the effect of lyophilizate collapse on pharmaceutically relevant proteins III: collapse during storage at elevated temperatures. Eur J Pharm Biopharm: Off J Arbeitsgemeinschaft Pharm Verfahrenstechnik. 2013;85(2):240–52.CrossRefGoogle Scholar
- 34.Parker A, Rigby-Singleton S, Perkins M, Bates D, Le Roux D, Roberts CJ, et al. Determination of the influence of primary drying rates on the microscale structural attributes and physicochemical properties of protein containing lyophilized products. J Pharm Sci. 2010;99(11):4616–29.CrossRefPubMedGoogle Scholar