Cargando…
The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG)
High protein concentration products for targeted therapeutic use are often freeze-dried to enhance stability. The long-term storage stability of freeze-dried (FD) plasma-derived Immunoglobulin G (IgG) from moderate to high concentrations (10–200 mg/mL) was assessed. Monomer content, binding activity...
Autores principales: | , , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
MDPI
2020
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238084/ https://www.ncbi.nlm.nih.gov/pubmed/32230795 http://dx.doi.org/10.3390/pharmaceutics12040303 |
_version_ | 1783536462334001152 |
---|---|
author | Duralliu, Arnold Matejtschuk, Paul Stickings, Paul Hassall, Laura Tierney, Robert Williams, Daryl R. |
author_facet | Duralliu, Arnold Matejtschuk, Paul Stickings, Paul Hassall, Laura Tierney, Robert Williams, Daryl R. |
author_sort | Duralliu, Arnold |
collection | PubMed |
description | High protein concentration products for targeted therapeutic use are often freeze-dried to enhance stability. The long-term storage stability of freeze-dried (FD) plasma-derived Immunoglobulin G (IgG) from moderate to high concentrations (10–200 mg/mL) was assessed. Monomer content, binding activity and reconstitution times were evaluated over a 12-month period under accelerated and real-term storage conditions. In the first case study it was shown that FD IgG from 10 to 200 mg/mL had minimal monomer/activity losses at up to ambient temperature after 12 months of storage. However, at 45 °C the sucrose-to-protein ratio played a significant impact on IgG stability above 50 mg/mL. All IgG concentrations witnessed moisture ingress over a 12-month period. The impact of moisture ingress from environmental exposure (between 0.1% and 5% w/w moisture) for IgG 50 mg/mL was assessed, being generated by exposing low moisture batches to an atmospheric environment for fixed time periods. Results showed that at −20 °C and 20 °C there was no significant difference in terms of monomer or antigen-binding activity losses over 6 months. However, at 45 °C, there were losses in monomer content, seemingly worse for higher moisture content samples although model binding activity indicated no losses. Finally, the difference between a low moisture product (0.1–1% w/w) and a moderately high moisture (3% w/w) product generated by alternative freeze-drying cycles, both stoppered under low oxygen headspace conditions, was evaluated. Results showed that at −20 °C and 20 °C there was no difference in terms of binding activity or monomer content. However, at 45 °C, the low moisture samples had greater monomer and binding activity losses than samples from the highest moisture cycle batch, indicating that over-drying can be an issue. |
format | Online Article Text |
id | pubmed-7238084 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2020 |
publisher | MDPI |
record_format | MEDLINE/PubMed |
spelling | pubmed-72380842020-05-28 The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG) Duralliu, Arnold Matejtschuk, Paul Stickings, Paul Hassall, Laura Tierney, Robert Williams, Daryl R. Pharmaceutics Article High protein concentration products for targeted therapeutic use are often freeze-dried to enhance stability. The long-term storage stability of freeze-dried (FD) plasma-derived Immunoglobulin G (IgG) from moderate to high concentrations (10–200 mg/mL) was assessed. Monomer content, binding activity and reconstitution times were evaluated over a 12-month period under accelerated and real-term storage conditions. In the first case study it was shown that FD IgG from 10 to 200 mg/mL had minimal monomer/activity losses at up to ambient temperature after 12 months of storage. However, at 45 °C the sucrose-to-protein ratio played a significant impact on IgG stability above 50 mg/mL. All IgG concentrations witnessed moisture ingress over a 12-month period. The impact of moisture ingress from environmental exposure (between 0.1% and 5% w/w moisture) for IgG 50 mg/mL was assessed, being generated by exposing low moisture batches to an atmospheric environment for fixed time periods. Results showed that at −20 °C and 20 °C there was no significant difference in terms of monomer or antigen-binding activity losses over 6 months. However, at 45 °C, there were losses in monomer content, seemingly worse for higher moisture content samples although model binding activity indicated no losses. Finally, the difference between a low moisture product (0.1–1% w/w) and a moderately high moisture (3% w/w) product generated by alternative freeze-drying cycles, both stoppered under low oxygen headspace conditions, was evaluated. Results showed that at −20 °C and 20 °C there was no difference in terms of binding activity or monomer content. However, at 45 °C, the low moisture samples had greater monomer and binding activity losses than samples from the highest moisture cycle batch, indicating that over-drying can be an issue. MDPI 2020-03-27 /pmc/articles/PMC7238084/ /pubmed/32230795 http://dx.doi.org/10.3390/pharmaceutics12040303 Text en © 2020 by the authors. Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (http://creativecommons.org/licenses/by/4.0/). |
spellingShingle | Article Duralliu, Arnold Matejtschuk, Paul Stickings, Paul Hassall, Laura Tierney, Robert Williams, Daryl R. The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG) |
title | The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG) |
title_full | The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG) |
title_fullStr | The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG) |
title_full_unstemmed | The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG) |
title_short | The Influence of Moisture Content and Temperature on the Long-Term Storage Stability of Freeze-Dried High Concentration Immunoglobulin G (IgG) |
title_sort | influence of moisture content and temperature on the long-term storage stability of freeze-dried high concentration immunoglobulin g (igg) |
topic | Article |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC7238084/ https://www.ncbi.nlm.nih.gov/pubmed/32230795 http://dx.doi.org/10.3390/pharmaceutics12040303 |
work_keys_str_mv | AT duralliuarnold theinfluenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT matejtschukpaul theinfluenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT stickingspaul theinfluenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT hassalllaura theinfluenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT tierneyrobert theinfluenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT williamsdarylr theinfluenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT duralliuarnold influenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT matejtschukpaul influenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT stickingspaul influenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT hassalllaura influenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT tierneyrobert influenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg AT williamsdarylr influenceofmoisturecontentandtemperatureonthelongtermstoragestabilityoffreezedriedhighconcentrationimmunoglobulingigg |