ArticlePharmaceutical research2016
Mutual Influence of Mannitol and Trehalose on Crystallization Behavior in Frozen Solutions.
Article in Pharmaceutical research, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Pooled it
- An Investigation of Water Vapor Sorption for Improving Reconstitution Pathways of Freeze-Dried Lipid Nanoparticles Stabilized by Trehalose/Mannitol Excipients.AAPS PharmSciTech · 2026Article
- Nanoparticulate protectants for the dry storage of protein therapeutics.Nanomedicine (London, England) · 2026Review
- Physicochemical Mechanisms of Protection Offered by Agarose Encapsulation during Cryopreservation of Mammalian Cells in the Absence of Membrane-Penetrating Cryoprotectants.ACS applied bio materials · 2023Article
- Alternative Excipients for Protein Stabilization in Protein Therapeutics: Overcoming the Limitations of Polysorbates.Pharmaceutics · 2022Review
- Synthesis and Application of Trehalose Materials.JACS Au · 2022Review
- Optimizing Effective Parameters to Enhance the Sensitivity of Vertical Flow Assay for Detection ofBiosensors · 2022Article
- Nanobubbles in Reconstituted Lyophilized Formulations: Interaction With Proteins and Mechanism of Formation.Journal of pharmaceutical sciences · 2020Article
- Characterizing modes of action and interaction for multicomponent osmolyte solutions on Jurkat cells.Biotechnology and bioengineering · 2019Article
- Metal-Organic Framework Encapsulation Preserves the Bioactivity of Protein Therapeutics.Advanced healthcare materials · 2018Article
- Detection of Collapse and Crystallization of Saccharide, Protein, and Mannitol Formulations by Optical Fibers in Lyophilization.Frontiers in chemistry · 2018Article
- Effects of Excipient Interactions on the State of the Freeze-Concentrate and Protein Stability.Pharmaceutical research · 2017Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
3 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposePhase separation of trehalose during freeze-drying could render it ineffective as a lyoprotectant. The bulking agent, mannitol, on the other hand, should crystallize readily upon freezing. It is therefore imperative to understand the mutual interaction of these sugars during freezing to ensure preservation of the API during freeze-drying.
methodsWe investigated the effect of mannitol to trehalose ratio (R) on the crystallization behavior of both solutes using Differential Scanning Calorimetry, X-Ray Crystallography and FTIR Spectrosopy during controlled freezing and annealing.
resultsWhen R = 1, crystallization of both mannitol (as hemihydrate) and trehalose (as α-anhydrate) were observed. When R ≥ 1, extent of mannitol crystallization was directly proportional to the value of R. When R < 1, trehalose completely suppressed mannitol crystallization. At R > 1, the freeze concentrate was heterogeneous and characterized by two glass transitions - the lower temperature transition (Tg") attributed to systems containing "extra" unfrozen water. When heated above Tg", crystallization of mannitol and the associated unfrozen water resulted in Tg' (glass transition temperature of the freeze-concentrate).
conclusionsR and not the total solute concentration, dictates the composition of the freeze concentrate as well as the physical stability of the excipients.
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