Stabilizers and their interaction with formulation components in frozen and freeze-dried protein formulations

Thakral, Seema; Sonje, Jayesh; Munjal, Bhushan; Suryanarayanan, Raj

doi:10.1016/j.addr.2021.03.003

Cited by 53 publications

(29 citation statements)

References 134 publications

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“…The cryoprotective behaviour of glycine stems also from its interaction with other ions and molecules in solution; the same interactinos that play an important role in the control of polymorphism of glycine on its crystallization. [328][329][330][331] Other applications of glycine are related to its ability to incorporate into the crystal lattices of other compounds, either as a co-former in salts or cocrystals, or as a guest-molecule incorporated into crystal lattices. As a salt-and cocrystal former with organic and inorganic compounds it finds applications in crystal enginnering, to give hundreds of versatile crystal structures, often polymorphic.…”

Section: Glycine and Its Ability To Form Solid Complexes With Other Compoundsmentioning

confidence: 99%

Glycine: The Gift that Keeps on Giving

Boldyreva

2021

Israel Journal of Chemistry

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Glycine is a small molecule. It cannot change its conformation and is achiral. Despite the apparent simplicity, glycine shows endless diversity in its behavior over many phenomena. It was the first amino acid for which polymorphism was reported, first on crystallization and then on hydrostatic compression. The polymorphs differ in their physical properties and their biological activity. Glycine clusters persist in solution, leading to "solution memory". Phenomena at interfaces are critically important for crystal growth, dissolution, and for physical properties, which can be at times unexpected, like polarity in centrosymmetric αpolymorph. It is a great pleasure to remind of these remarkable phenomena in a special issue honoring professors Meir Lahav and Leslie Leiserowitz, who pioneered the study of the behavior of this unique molecule in many respects, and showed how complex and non-trivial phenomena can be at interfaces: between phases and between research fields.

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Section: Glycine and Its Ability To Form Solid Complexes With Other Compoundsmentioning

confidence: 99%

Glycine: The Gift that Keeps on Giving

Boldyreva

2021

Israel Journal of Chemistry

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“… Goshima et al (2016) have shown that inclusion of NaCl may improve the stability of freeze-dried model protein albumin. Thakral et al (2021) have systematically reviewed the interactions between formulation components both in frozen and freeze-dried systems.…”

Section: Discussionmentioning

confidence: 99%

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Matejtschuk

Bird²,

Ezeajughi³

et al. 2022

Front. Mol. Biosci.

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Formulation is critical to successful delivery of lyophilized biologics. We have compared the impact of buffer choice and the addition of sodium chloride (a formulant often viewed as unfavorable for freeze-drying applications) on the outcome of trial lyophilization of an interleukin-6 reference material. While phosphate buffer was a preferred choice and yielded well-formed cakes associated with fair recovery of biological activity, the resultant residual moisture content was high (2–4% w/w). By inclusion of isotonic levels of NaCl, the freeze-dried appearance and process were not impaired, but the residual moisture delivered was considerably reduced to levels <1% w/w. We postulate that this is due to the presence of a more open-cake structure and support this with evidence from thermal analysis and scanning electron microscopy. This work illustrates the importance of wide ranging empirical investigation of formulation options in order to optimize freeze-drying outcomes for biologics.

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“…High Tg may contribute to maintaining the freeze-dried ld LDH in a stable, glassified state during storage [ 43 , 44 ]. Additionally, the observed decline in protective action may result from a greater tendency to undergo phase separation compared with sucrose and asparagine [ 45 , 46 ]. Furthermore, additional stress factors during storage, such as unintended temperature excursions, may result in different protective effects between freeze-drying and long-term storage [ 46 ].…”

Section: Discussionmentioning

confidence: 99%

Enzymatic characterization of D-lactate dehydrogenase and application in alanine aminotransferase activity assay kit

2021

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D-lactate dehydrogenase (D-LDH) is widely used for the clinical detection of alanine aminotransferase (ALT) activity. It is a key enzyme in ALT detection kits, and its enzymatic properties directly determine sensitivity and accuracy of such kits. In this study, D-lactate dehydrogenase (WP_011543503, ldLDH) coding sequence derived from Lactobacillus delbrueckii was obtained from the NCBI database by gene mining. LdLDH was expressed and purified in Escherichia coli, and its enzyme activity, kinetic parameters, optimum temperature, and pH were characterized. Furthermore, stabilizers, including sugars, polyols, amino acids, certain salts, proteins, and polymers, were screened to improve stability of ldLDH during freeze-drying and storage. Finally, a kit based on ldLDH was tested to determine whether the enzyme had potential clinical applications. The results showed that ldLDH had a specific activity of 1,864 U/mg, K m value of 1.34 mM, optimal reaction temperature of 55°C, and an optimal pH between 7.0 and 7.5. When sucrose or asparagine was used as a stabilizer, freeze-dried ldLDH remained stable at 37°C for > 2 months without significant loss of enzymatic activity. These results indicated that ldLDH possesses high activity and stability. Test results using the ALT assay kit prepared with ldLDH were consistent with those of commercial kits, with a relative deviation <5%. These results indicated that ldLDH met the primary requirements for ALT assays, laying a foundation for the development of new ALT kits with potential clinical applications.

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Stabilizers and their interaction with formulation components in frozen and freeze-dried protein formulations

Cited by 53 publications

References 134 publications

Glycine: The Gift that Keeps on Giving

Glycine: The Gift that Keeps on Giving

Impact of Formulation Choices on the Freeze-Drying of an Interleukin-6 Reference Material

Enzymatic characterization of D-lactate dehydrogenase and application in alanine aminotransferase activity assay kit

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