Mechanical compression affecting the thermal-induced conformational stability and denaturation temperature of human fibrinogen

Lin, Shan‐Yang; Hsieh, Tzu-Feng; Wei, Yen-Shan; Li, Mei-Jane

doi:10.1016/j.ijbiomac.2005.09.008

Cited by 6 publications

(5 citation statements)

References 41 publications

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“…The compression of biologics is a relatively new but critical unit operation with the potential to cause physical degradation of proteins/ peptides because of exposure to mechanical, thermal, and shear stresses. 20,21 Finally, third is the enteric coating of tablets to protect the active pharmaceutical ingredient (API) from degradation in the upper GI tract. The polymeric enteric coating has been well established for lower molecular weight APIs but only successfully applied to biologics in a few cases (e.g., adenovirus vaccine tablets).…”

Section: ■ Introductionmentioning

confidence: 99%

“…First is the drying of proteins/peptides into solids, which is currently achievable at large scale by lyophilization, spray drying, or foam drying. − The aseptic spray drying technique also enables powder engineering of biologics. − Second is the compression of biologics, with or without excipients, into tablets. The compression of biologics is a relatively new but critical unit operation with the potential to cause physical degradation of proteins/peptides because of exposure to mechanical, thermal, and shear stresses. , Finally, third is the enteric coating of tablets to protect the active pharmaceutical ingredient (API) from degradation in the upper GI tract. The polymeric enteric coating has been well established for lower molecular weight APIs but only successfully applied to biologics in a few cases (e.g., adenovirus vaccine tablets). − …”

Section: Introductionmentioning

confidence: 99%

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Developing Biologics Tablets: The Effects of Compression on the Structure and Stability of Bovine Serum Albumin and Lysozyme

et al. 2019

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Oral administration is advantageous compared to the commonly used parenteral administration for local therapeutic uses of biologics or mucosal vaccines, since it can specifically target the gastrointestinal (GI) tract. It offers better patient compliance, even though the general use of such a delivery route is often limited by potential drug degradation in the GI tract and poor absorption. Using bovine serum albumin (BSA) and lysozyme as two model proteins, we studied their solid-state properties, mechanical properties, and tabletability as well as effects of compaction pressure, particle size, and humidity on protein degradation. It was found that BSA and lysozyme are highly hygroscopic, and their tablet manufacturability (powder caking, punch sticking, and tablet lamination) is sensitive to the humidity. BSA and lysozyme exhibited high plasticity and excellent tabletability and remained amorphous at high pressure and humidity. As for protein stability, lysozyme was resistant to high pressure (up to 300 MPa) and high humidity (up to 93%). In contrast, BSA underwent aggregation upon compression, an effect that was more pronounced for smaller BSA particles. High humidity accelerated the aggregation of BSA during incubation, but it did not further synergize with mechanical stress to induce protein degradation. Thus, compression can potentially induce protein aggregation, but this effect is protein-dependent. Therefore, strategies (e.g., the use of excipients, optimized manufacturing processes) to inhibit protein degradation should be explored before their tablet dosage form development.

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Section: ■ Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Developing Biologics Tablets: The Effects of Compression on the Structure and Stability of Bovine Serum Albumin and Lysozyme

et al. 2019

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“…Even though the melting point of fibrinogen could not be determined in solution with DLS, there are a number of reports demonstrated that fibrinogen is very sensitive to heat and its structure shows dramatic changes between 60°C and 70°C. 52,53 Figure 4(a) shows the SERS spectra of fibrinogen with temperature gradient and Fig. 4(b) shows the 2-D Euclidean distances plot.…”

Section: Resultsmentioning

confidence: 99%

Label-free detection of proteins in ternary mixtures using surface-enhanced Raman scattering and protein melting profiles

et al. 2013

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ABSTRACT. The multiplex detection of biologically important molecules such as proteins in complex mixtures has critical importance not only in disease diagnosis but also in other fields such as proteomics and biotechnology. Surface-enhanced Raman scattering (SERS) is a powerful technique for multiplex identification of molecular components in a mixture. We combined the multiplexing power of SERS and heat denaturation of proteins to identify proteins in ternary protein mixtures. The heat denaturation profiles of four model blood proteins, transferrin, human serum albumin, fibrinogen, and hemoglobin, were studied with SERS. Then, two ternary mixtures of these four proteins were used to test the feasibility of the approach. It was demonstrated that unique denaturation profiles of each protein could be used for their identification in the mixture.

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“…Thus, to thoroughly evaluate tableting as a formulation process for biopharmaceuticals, it is necessary to investigate if the pressure during compaction induces changes in the susceptibility of protein APIs toward denaturation caused by the environmental conditions, such as elevated temperature during ingestion and reconstitution. In this context, the transition temperature ( T m ) of unfolding, a parameter indicative for the thermal stability of proteins, has been reported to be significantly reduced for proteins in the solid state as well as for reconstituted formulations as a result of stress applied during pharmaceutical processing . Interestingly, Elkordy et al showed that although spray‐drying leads to a decrease in the T m of reconstituted DNase I by 5.3°C, no marked changes were found in the secondary structure of the reconstituted processed protein compared with its initial form.…”

Section: Introductionmentioning

confidence: 99%

Influence of Tableting on the Conformation and Thermal Stability of Trypsin as a Model Protein

Klukkert¹,

Weert

Fano

et al. 2015

Journal of Pharmaceutical Sciences

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Mechanical compression affecting the thermal-induced conformational stability and denaturation temperature of human fibrinogen

Cited by 6 publications

References 41 publications

Developing Biologics Tablets: The Effects of Compression on the Structure and Stability of Bovine Serum Albumin and Lysozyme

Developing Biologics Tablets: The Effects of Compression on the Structure and Stability of Bovine Serum Albumin and Lysozyme

Label-free detection of proteins in ternary mixtures using surface-enhanced Raman scattering and protein melting profiles

Influence of Tableting on the Conformation and Thermal Stability of Trypsin as a Model Protein

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