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. 2012 Jan 1;3(1):55-63.
doi: 10.1364/BOE.3.000055. Epub 2011 Dec 7.

Optical coherence tomography-based freeze-drying microscopy

Mircea Mujat  1 , Kristyn Greco, Kristin L Galbally-Kinney, Daniel X Hammer, R Daniel Ferguson, Nicusor Iftimia, Phillip Mulhall, Puneet Sharma, Michael J Pikal, William J Kessler
Affiliations

Optical coherence tomography-based freeze-drying microscopy

Mircea Mujat et al. Biomed Opt Express. .

Abstract

A new type of freeze-drying microscope based upon time-domain optical coherence tomography is presented here (OCT-FDM). The microscope allows for real-time, in situ 3D imaging of pharmaceutical formulations in vials relevant for manufacturing processes with a lateral resolution of <7 μm and an axial resolution of <5 μm. Correlation of volumetric structural imaging with product temperature measured during the freeze-drying cycle allowed investigation of structural changes in the product and determination of the temperature at which the freeze-dried cake collapses. This critical temperature is the most important parameter in designing freeze-drying processes of pharmaceutical products.

Keywords: (110.0180) Microscopy; (110.4500) Optical coherence tomography; (180.6900) Three-dimensional microscopy.

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Figures

Fig. 1
Fig. 1
TDOCT setup. SLD – 1300 nm superluminescent diode; DET—balance detector; AOM—acousto-optic modulator; Circ—circulator; Col—collimator; R—retroreflector; Obj—microscope objective; Scan—scanning optics; 90/10 and 50/50 fiber beamsplitters.
Fig. 2
Fig. 2
(a) Fiber-optic based interferometer and (b) the scanning optics.
Fig. 3
Fig. 3
(a) Zemax optical design and (b) SolidWorks mechanical design.
Fig. 4
Fig. 4
2D cross-sections of 5% sucrose freeze-dried in a vial, (a)x-y view (Media 1), and (b) z-y view (Media 2); (c) time evolution of the freeze-drying process in a 3D representation (Media 3).
See this image and copyright information in PMC

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