1. Academic Validation
  2. Isomalt and its diastereomer mixtures as stabilizing excipients with freeze-dried lactate dehydrogenase

Isomalt and its diastereomer mixtures as stabilizing excipients with freeze-dried lactate dehydrogenase

  • Int J Pharm. 2018 Mar 1;538(1-2):287-295. doi: 10.1016/j.ijpharm.2018.01.015.
Anna-Kaisa Tuderman 1 Clare J Strachan 2 Anne M Juppo 3
Affiliations

Affiliations

  • 1 Formulation and Industrial Pharmacy, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. Electronic address: anna-kaisa.koskinen@helsinki.fi.
  • 2 Formulation and Industrial Pharmacy, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. Electronic address: clare.strachan@helsinki.fi.
  • 3 Formulation and Industrial Pharmacy, Division of Pharmaceutical Chemistry and Technology, Faculty of Pharmacy, University of Helsinki, Helsinki, Finland. Electronic address: anne.juppo@helsinki.fi.
Abstract

The purpose of this research was to study isomalt as a protein-stabilizing excipient with Lactate Dehydrogenase (LDH) during freeze-drying and subsequent storage and compare it to sucrose, a standard freeze-drying excipient. Four different diastereomer mixtures of isomalt were studied. The stability of the protein was studied with a spectrophotometric Enzyme activity test and circular dichroism after freeze-drying and after 21 days of storage at 16% RH. Physical stability was analyzed with differential scanning calorimetry and Karl Fischer titration. Statistical analysis was utilized in result analysis. LDH activity was almost completely retained after freeze-drying with sucrose; whereas samples stabilized with isomalt diastereomer mixtures had a considerably lower protein activity. During storage the sucrose-containing samples lost most of their enzymatic activity, while the isomalt mixtures retained the protein activity better. In all cases changes to protein secondary structure were observed. Isomalt diastereomer mixtures have some potential as protein-stabilizing excipients during freeze-drying and subsequent storage. Isomalt stabilized LDH moderately during freeze-drying; however it performed better during storage. Future studies with other proteins are required to evaluate more generally whether isomalt would be a suitable excipient for pharmaceutical freeze-dried protein formulations.

Keywords

Freeze-drying; Isomalt; Lactate dehydrogenase; Protein stabilization; Sucrose.

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