Thermally Induced Denaturation of Lyophilized Bovine Somatotropin and Lysozyme As Impacted by Moisture and Excipients

Bell, Leonard N.; Hageman, Michael J.; Muraoka, Lee M.

doi:10.1002/jps.2600840608

Cited by 97 publications

(85 citation statements)

References 27 publications

(9 reference statements)

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“…DSC results show that the protein unfolding temperature in solids increases at lower residual moisture levels (47). However, it is thought that protein molecules need at least a monolayer of water molecules to retain their essential conformational structure in the dried state, probably by satisfying hydrogen bonding of the surface groups (48).…”

Section: 221mentioning

confidence: 98%

Stabilisation of biopharmaceutical products and finished product formulations

Hora¹,

Chen²

1999

Biopharmaceuticals, an Industrial Perspective

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Abstract:This chapter overviews the stabilization of protein-based biophannaceuticals. Finished biophannaceutical products must have the required stability from a clinical and regulatory point of view. Furthermore, the stability profile should cover the manufacturing and marketing cycles of the product to minimise costs. The major routes by which proteins may be degraded are outlined. A brief description ofbiophannaceutical production processes is provided to acquaint the reader with issues relating to stabilisation during processing. The basic principles of how in-process material and finished product may be stabilized are presented. F inaUy, a table of major constituents in approved biophannaceuticals is included at the end of the chapter to illustrate how stabilisation principles have been put to practice to date.

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Section: 221mentioning

confidence: 98%

Stabilisation of biopharmaceutical products and finished product formulations

Hora¹,

Chen²

1999

Biopharmaceuticals, an Industrial Perspective

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“…However, at least in the systems studied, T m decreases with the addition of sugars to the protein formulations. 22,[24][25][26] A linear correlation was found between the intensity of the a-helical band (obtained using second derivative FTIR) and the melting enthalpy DH m of spray-dried lysozyme. 21 Therefore, DH m may be a useful parameter to evaluate protein structure, and therefore, also may be a measure of stability in the solid state.…”

Section: Denaturationmentioning

confidence: 99%

“…That is, the higher the T m , the more thermodynamically stable is the protein. [21][22][23] However, it must be noted that the relative T m only provides the thermodynamic stability of the protein near T m . The relative thermodynamic stability for a series of samples at low temperature, that is, the storage temperature, may be different from the relative stability at T m .…”

Section: Denaturationmentioning

confidence: 99%

Mechanisms of protein stabilization in the solid state

Chang

Pikal

2009

Journal of Pharmaceutical Sciences

270

208

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“…This was confirmed by the thermogravimetric analysis; the water content of lyophilised DNase I as received (11.21 ± 0.47%, w/w) was significantly higher (p < 0.05) than that of the spray-dried protein (6.08 ± 0.39%, w/w). This may explain the higher stability of solid-state spray-dried DNase I over that of as received protein; as moisture increased, thermal stability decreased (Bell et al, 1995). Raised water content leads to increasing molecular mobility (Tzannis and Prestrelski, 1999) and hence decreased thermal stability or T m .…”

Section: Differential Scanning Calorimetry (Dsc)mentioning

confidence: 99%

Study of protein conformational stability and integrity using calorimetry and FT-Raman spectroscopy correlated with enzymatic activity

Elkordy

Forbes²,

Barry³

2008

European Journal of Pharmaceutical Sciences

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Enzymatic assay after cooling of thermally denatured protein solutions from HSDSC determined if thermal transition reversibility was related to biological activity. HSDSC data showed that molecules from lyophilised lysozyme were able to refold better than the spraydried form. This was confirmed by enzymatic assay. Moreover, enzymatic assay results revealed that lysozyme folding reversibility was related to the native structure of the protein that is essential for the biological activity.Thermal denaturation of DNase I and LDH samples in HSDSC was not reversible upon cooling of thermally denatured proteins (in contrast to lysozyme). Hence, it was decided to identify the effect of protein initial structures on its propensity to thermal denaturation via FT-Raman spectroscopy. In other words, proteins may denature with structural alterations due to stresses such as heat and the protein loses its enzymatic activity. Consequently, FTRaman investigated the effects of spray drying and heating of solid DNase I and LDH samples, from differential scanning calorimetry, on protein conformational integrities. Lyophilised and spray-dried DNase I and LDH solid samples were heated to two temperatures, one before the apparent denaturation temperatures (T m ) and the other after the T m . Samples heated below their T m showed some alterations of the secondary structure and some enzy- IntroductionProteins fold in three dimensions. Protein structure is organised from primary structure to quaternary structure. primary structure or the amino acid sequence of the peptide chains is the ultimate determinant for the protein native form. The protein secondary structure is the assignment of ␣-helices and ␤-sheets along the main peptide chain; whilst the ter-0928-0987/$ -see front matter

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Thermally Induced Denaturation of Lyophilized Bovine Somatotropin and Lysozyme As Impacted by Moisture and Excipients

Cited by 97 publications

References 27 publications

Stabilisation of biopharmaceutical products and finished product formulations

Stabilisation of biopharmaceutical products and finished product formulations

Mechanisms of protein stabilization in the solid state

Study of protein conformational stability and integrity using calorimetry and FT-Raman spectroscopy correlated with enzymatic activity

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