| People | Locations | Statistics |
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| Naji, M. |
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| Motta, Antonella |
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| Aletan, Dirar |
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| Mohamed, Tarek |
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| Ertürk, Emre |
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| Taccardi, Nicola |
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| Kononenko, Denys |
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| Petrov, R. H. | Madrid |
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| Alshaaer, Mazen | Brussels |
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| Bih, L. |
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| Casati, R. |
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| Muller, Hermance |
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| Kočí, Jan | Prague |
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| Šuljagić, Marija |
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| Kalteremidou, Kalliopi-Artemi | Brussels |
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| Azam, Siraj |
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| Ospanova, Alyiya |
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| Blanpain, Bart |
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| Ali, M. A. |
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| Popa, V. |
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| Rančić, M. |
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| Ollier, Nadège |
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| Azevedo, Nuno Monteiro |
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| Landes, Michael |
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| Rignanese, Gian-Marco |
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Hinrichs, Wouter
University of Groningen
in Cooperation with on an Cooperation-Score of 37%
Topics
Publications (17/17 displayed)
- 2024Combinations of arginine and pullulan reveal the selective effect of stabilization mechanisms on different lyophilized proteinscitations
- 2018The mechanism behind the biphasic pulsatile drug release from physically mixed poly(DL-lactic(-co-glycolic) acid)-based compactscitations
- 2016Compacted Solid Dosage Form
- 2015Protein release from water-swellable poly(d,l-lactide-PEG)-b-poly(ϵ-caprolactone) implantscitations
- 2015Protein Stability during Hot Melt Extrusion
- 2015Size and molecular flexibility of sugars determine the storage stability of freeze-dried proteinscitations
- 2015Protein Stability during Hot Melt Extrusion: The Effect of Extrusion Temperature, Hydrophilicity of Polymers and Sugar Glass Pre-stabilization
- 2015Polymeric formulations for drug release prepared by hot melt extrusioncitations
- 2013Designing CAF-adjuvanted dry powder vaccinescitations
- 2013Unraveling protein stabilization mechanismscitations
- 2012Preparation and physicochemical evaluation of a new tacrolimus tablet formulation for sublingual administrationcitations
- 2010Effect of drug-carrier interaction on the dissolution behavior of solid dispersion tabletscitations
- 2006Characterization of the molecular distribution of drugs in glassy solid dispersions at the nano-meter scale, using differential scanning calorimetry and gravimetric water vapour sorption techniquescitations
- 2005Inulin is a promising cryo- and lyoprotectant for PEGylated lipoplexescitations
- 2004Incorporation of lipophilic drugs in sugar glasses by lyophilization using a mixture of water and tertiary butyl alcohol as solventcitations
- 2003Investigations into the stabilization of drugs by sugar glassescitations
- 2001Inulin glasses for the stabilization of therapeutic proteinscitations
Places of action
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article
Size and molecular flexibility of sugars determine the storage stability of freeze-dried proteins
Abstract
Protein-based biopharmaceuticals are generally produced as aqueous solutions and stored refrigerated to obtain sufficient shelf life. Alternatively, proteins may be freeze-dried in the presence of sugars to allow storage stability at ambient conditions for prolonged periods. However, to act as a stabilizer, these sugars should remain in the glassy state during storage. This requires a sufficiently high glass transition temperature (Tg). Furthermore, the sugars should be able to replace the hydrogen bonds between the protein and water during drying. Frequently used disaccharides are characterized by a relatively low Tg, rendering them sensitive to plasticizing effects of residual water, which strongly reduces the Tgvalues of the formulation. Larger sugars generally have higher Tgs, but it is assumed that these sugars are limited in their ability to interact with the protein due to steric hindrance. In this paper, the size and molecular flexibility of sugars was related to their ability to stabilize proteins. Four diverse proteins varying in size from 6 kDa to 540 kDa were freeze-dried in the presence of different sugars varying in size and molecular flexibility. Subsequently, the different samples were subjected to an accelerated stability test. Using protein specific assays and intrinsic fluorescence, stability of the proteins was monitored. It was found that the smallest sugar (disaccharide trehalose) best preserved the proteins, but also that the Tgof the formulations was only just high enough to maintain sufficient vitrification. When trehalose-based formulations are exposed to high relative humidities, water uptake by the product reduces the Tgs too much. In that respect, sugars with higher Tgs are desired. Addition of polysaccharide dextran 70 kDa to trehalose greatly increased the Tgof the formulation. Moreover, this combination also improved the stability of the proteins compared to dextran only formulations. The molecularly flexible oligosaccharide inulin 4 kDa provided better stabilization than the similarly sized but molecularly rigid oligosaccharide dextran 6 kDa. In conclusion, the results of this study indicate that size and molecular flexibility of sugars affect their ability to stabilize proteins. As long as they maintain vitrified, smaller and molecularly more flexible sugars are less affected by steric hindrance and thus better capable at stabilizing proteins.