Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations
Microwave-assisted freeze-drying (MFD) offers significant time savings compared to conventional freeze-drying (CFD). While a few studies have investigated the stability of biopharmaceuticals with low protein concentrations after MFD and storage, the impact of MFD on high-concentration monoclonal ant...
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| Format: | Article |
| Language: | English |
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MDPI AG
2023-12-01
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| Series: | Pharmaceutics |
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| Online Access: | https://www.mdpi.com/1999-4923/15/12/2783 |
| _version_ | 1797379659439013888 |
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| author | Nicole Härdter Raimund Geidobler Ingo Presser Gerhard Winter |
| author_facet | Nicole Härdter Raimund Geidobler Ingo Presser Gerhard Winter |
| author_sort | Nicole Härdter |
| collection | DOAJ |
| description | Microwave-assisted freeze-drying (MFD) offers significant time savings compared to conventional freeze-drying (CFD). While a few studies have investigated the stability of biopharmaceuticals with low protein concentrations after MFD and storage, the impact of MFD on high-concentration monoclonal antibody (mAb) formulations remains unclear. In this study, we systematically examined the effect of protein concentration in MFD and assessed protein stability following MFD, CFD, and subsequent storage using seven protein formulations with various stabilizers and concentrations. We demonstrated that microwaves directly interact with the active pharmaceutical ingredient (API), leading to decreased physical stability, specifically aggregation, in high-concentration antibody formulations. Furthermore, typically used sugar:protein ratios from CFD were insufficient for stabilizing mAbs when applying microwaves. We identified the intermediate drying phase as the most critical for particle formation, and cooling the samples provided some protection for the mAb. Our findings suggest that MFD technology may not be universally applicable to formulations well tested in CFD and could be particularly beneficial for formulations with low API concentrations requiring substantial amounts of glass-forming excipients, such as vaccines and RNA-based products. |
| first_indexed | 2024-03-08T20:26:15Z |
| format | Article |
| id | doaj.art-9aa49e8e48554893afb0b1f816931131 |
| institution | Directory Open Access Journal |
| issn | 1999-4923 |
| language | English |
| last_indexed | 2024-03-08T20:26:15Z |
| publishDate | 2023-12-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Pharmaceutics |
| spelling | doaj.art-9aa49e8e48554893afb0b1f8169311312023-12-22T14:32:20ZengMDPI AGPharmaceutics1999-49232023-12-011512278310.3390/pharmaceutics15122783Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody FormulationsNicole Härdter0Raimund Geidobler1Ingo Presser2Gerhard Winter3Department of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Pharmaceutical Development Biologicals, 88397 Biberach an der Riß, GermanyBoehringer Ingelheim Pharma GmbH & Co. KG, Pharmaceutical Development Biologicals, 88397 Biberach an der Riß, GermanyDepartment of Pharmacy, Pharmaceutical Technology and Biopharmaceutics, Ludwig-Maximilians-Universität München, 81377 Munich, GermanyMicrowave-assisted freeze-drying (MFD) offers significant time savings compared to conventional freeze-drying (CFD). While a few studies have investigated the stability of biopharmaceuticals with low protein concentrations after MFD and storage, the impact of MFD on high-concentration monoclonal antibody (mAb) formulations remains unclear. In this study, we systematically examined the effect of protein concentration in MFD and assessed protein stability following MFD, CFD, and subsequent storage using seven protein formulations with various stabilizers and concentrations. We demonstrated that microwaves directly interact with the active pharmaceutical ingredient (API), leading to decreased physical stability, specifically aggregation, in high-concentration antibody formulations. Furthermore, typically used sugar:protein ratios from CFD were insufficient for stabilizing mAbs when applying microwaves. We identified the intermediate drying phase as the most critical for particle formation, and cooling the samples provided some protection for the mAb. Our findings suggest that MFD technology may not be universally applicable to formulations well tested in CFD and could be particularly beneficial for formulations with low API concentrations requiring substantial amounts of glass-forming excipients, such as vaccines and RNA-based products.https://www.mdpi.com/1999-4923/15/12/2783freeze-dryinglyophilizationmicrowaveproteinmonoclonal antibodystability |
| spellingShingle | Nicole Härdter Raimund Geidobler Ingo Presser Gerhard Winter Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations Pharmaceutics freeze-drying lyophilization microwave protein monoclonal antibody stability |
| title | Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations |
| title_full | Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations |
| title_fullStr | Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations |
| title_full_unstemmed | Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations |
| title_short | Microwave-Assisted Freeze–Drying: Impact of Microwave Radiation on the Quality of High-Concentration Antibody Formulations |
| title_sort | microwave assisted freeze drying impact of microwave radiation on the quality of high concentration antibody formulations |
| topic | freeze-drying lyophilization microwave protein monoclonal antibody stability |
| url | https://www.mdpi.com/1999-4923/15/12/2783 |
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