Well-plate freeze-drying: a high throughput platform for screening of physical properties of freeze-dried formulations

Abstract

Context: Freeze-drying in presence of excipients is a common practice to stabilize biomacromolecular formulations. The composition of this formulation is known to affect the quality of the final product.

Objective: The aim of this study was to evaluate freeze-drying in well-plates as a high throughput platform for formulation screening of freeze-dried products.

Methods: Model formulations consisting of mannitol, sucrose and bovine serum albumin were freeze-dried in brass well plates, plastic well plates and vials. Physical properties investigated were solid form, residual moisture, cake collapse and reconstitution time.

Results: Samples freeze-dried in well-plates had an acceptable visual cake appearance. Solid form analysis by high throughput X-ray powder diffraction indicated comparable polymorphic outcome independent of the container. The expected increase in moisture level due to increasing amount of amorphous matter in the samples was observed in both vials and well plates. Cake collapse was found to be representative in well plates and could be effectively quantified using image analysis. Reconstitution time was also found to be equal in all three platforms. Finally no significant edge effect was found for any of the quality attributes analyzed.

Conclusion: Freeze-drying in well-plates was found to be a suitable and representative high throughput platform for formulation screening.

• Cake collapse
• formulation development
• freeze-drying
• high throughput screening
• reconstitution time
• solid state

Acknowledgements

The authors would like to thank Jian Wu for development of Matlab scripts used for image analysis. We would also like to thank Celia Sloth-Lisbjerg for the preliminary studies.

Declaration of interest

Funding from the Danish Council for Independent Research, Medical Sciences, is acknowledged (H.T.). The grant from Lundbeckfonden for the purchase of the X-ray powder diffractometer (grant decision 479/06) and a grant from Carlsbergfondet for the purchase of the freeze-dryer financially contributed in this work.