ArticlePharmaceutical research2007
Sorbitol crystallization can lead to protein aggregation in frozen protein formulations.
Article in Pharmaceutical research, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers, 1 of them a synthesis that pooled it.
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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
18 citing papers in PubMed, 1 synthesis or guideline pooled it, 100 citations in OpenAlex.
- Pooled it
- Preliminary Exploration on the Regulatory Mechanism of Ionic Strength on Conformation and Hydration of Silver Carp Myosin.Foods (Basel, Switzerland) · 2025Article
- Practical advice in the development of a lyophilized protein drug product.Antibody therapeutics · 2025Review
- Effect of Buffer Salts on Physical Stability of Lyophilized and Spray-Dried Protein Formulations Containing Bovine Serum Albumin and Trehalose.Pharmaceutical research · 2023Article
- Alternative Excipients for Protein Stabilization in Protein Therapeutics: Overcoming the Limitations of Polysorbates.Pharmaceutics · 2022Review
- Formulation and efficacy of ECO/pRHO-ABCA4-SV40 nanoparticles for nonviral gene therapy of Stargardt disease in a mouse model.Journal of controlled release : official journal of the Controlled Release Society · 2021Article
- Characterizing and Minimizing Aggregation and Particle Formation of Three Recombinant Fusion-Protein Bulk Antigens for Use in a Candidate Trivalent Rotavirus Vaccine.Journal of pharmaceutical sciences · 2020Article
- Interfacial Stress in the Development of Biologics: Fundamental Understanding, Current Practice, and Future Perspective.The AAPS journal · 2019Article
- Article
- Mutual Influence of Mannitol and Trehalose on Crystallization Behavior in Frozen Solutions.Pharmaceutical research · 2016Article
- Stabilization of proteins in solid form.Advanced drug delivery reviews · 2015Review
- Microheterogeneity in frozen protein solutions.International journal of pharmaceutics · 2015Article
- Ultrasonication as a potential tool to predict solute crystallization in freeze-concentrates.Pharmaceutical research · 2014Article
- Beyond glass transitions: studying the highly viscous and elastic behavior of frozen protein formulations using low temperature rheology and its potential implications on protein stability.Pharmaceutical research · 2013Article
- Frozen state storage instability of a monoclonal antibody: aggregation as a consequence of trehalose crystallization and protein unfolding.Pharmaceutical research · 2011Article
- Effects of glycosylation on the stability of protein pharmaceuticals.Journal of pharmaceutical sciences · 2009Review
- Microcalorimetry: a response to challenges in modern biotechnology.Microbial biotechnology · 2008Review
- Preliminary Assessment of Various Additives on the Specific Reactivity of Anti- rHBsAg Monoclonal Antibodies.Avicenna journal of medical biotechnologyArticle
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
purposeThis work examines the cause of aggregation of an Fc-fusion protein formulated in sorbitol upon frozen storage for extended periods of time at -30 degrees C. MATERIALS AND
methodsWe designed sub-ambient differential scanning calorimetry (DSC) experiments to capture the effects of long-term frozen storage. The physical stability of formulation samples was monitored by size exclusion high performance liquid chromatography (SE-HPLC).
resultsDSC analysis of non-frozen samples shows the expected glass transitions (Tg') at -45 degrees C for samples in sorbitol and at -32 degrees C in sucrose. In time course studies where sorbitol formulations were stored at -30 degrees C and analyzed by DSC without thawing, two endothermic transitions were observed: a melting endotherm at -20 degrees C dissipated over time, and a second endotherm at -8 degrees C was seen after approximately 2 weeks and persisted in all later time points. Protein aggregation was only seen in the samples formulated in sorbitol and stored at -30 degrees C, correlating aggregation with the aforementioned melts.
conclusionsThe observed melts are characteristic of crystalline substances and suggest that the sorbitol crystallizes over time. During freezing, the excipient must remain in the same phase as the protein to ensure protein stability. By crystallizing, the sorbitol is phase-separated from the protein, which leads to protein aggregation.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.