Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations
In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., -6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation.
| Medienart: |
E-Artikel |
|---|
| Erscheinungsjahr: |
2024 |
|---|---|
| Erschienen: |
2024 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:21 |
|---|---|
| Enthalten in: |
Molecular pharmaceutics - 21(2024), 4 vom: 01. Apr., Seite 1691-1704 |
| Sprache: |
Englisch |
|---|
| Beteiligte Personen: |
Gao, Han [VerfasserIn] |
|---|
| Links: |
|---|
| Themen: |
2P471X1Z11 |
|---|
| Anmerkungen: |
Date Completed 03.04.2024 Date Revised 03.04.2024 published: Print-Electronic Citation Status MEDLINE |
|---|
| doi: |
10.1021/acs.molpharmaceut.3c00991 |
|---|
| funding: |
|
|---|---|
| Förderinstitution / Projekttitel: |
|
| PPN (Katalog-ID): |
NLM369200659 |
|---|
| LEADER | 01000caa a22002652 4500 | ||
|---|---|---|---|
| 001 | NLM369200659 | ||
| 003 | DE-627 | ||
| 005 | 20240403235550.0 | ||
| 007 | cr uuu---uuuuu | ||
| 008 | 240302s2024 xx |||||o 00| ||eng c | ||
| 024 | 7 | |a 10.1021/acs.molpharmaceut.3c00991 |2 doi | |
| 028 | 5 | 2 | |a pubmed24n1363.xml |
| 035 | |a (DE-627)NLM369200659 | ||
| 035 | |a (NLM)38430187 | ||
| 040 | |a DE-627 |b ger |c DE-627 |e rakwb | ||
| 041 | |a eng | ||
| 100 | 1 | |a Gao, Han |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Effect of Annealing on Visible-Bubble Formation and Stability Profiles of Freeze-Dried High Concentration Omalizumab Formulations |
| 264 | 1 | |c 2024 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
| 338 | |a ƒa Online-Ressource |b cr |2 rdacarrier | ||
| 500 | |a Date Completed 03.04.2024 | ||
| 500 | |a Date Revised 03.04.2024 | ||
| 500 | |a published: Print-Electronic | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a In the clinical application of freeze-dried highly concentrated omalizumab formulations, extensive visible bubbles (VBs) can be generated and remain for a long period of time in the reconstitution process, which greatly reduces the clinical use efficiency. It is necessary to understand the forming and breaking mechanism of VBs in the reconstitution process, which is a key factor for efficient and safe administration of biopharmaceutical injection. The effects of different thermal treatments on the volume of VBs and stability of omalizumab, mAb-1, and mAb-2 were investigated. The internal microvoids of the cake were characterized by scanning electron microscopy and mercury intrusion porosimetry. Electron paramagnetic resonance was applied to obtain the molecular mobility of the protein during annealing. A large number of VBs were generated in the reconstitution process of unannealed omalizumab and remained for a long period of time. When annealing steps were added, the volume of VBs was dramatically reduced. When annealed at an aggressive temperature (i.e., -6 °C), although the volume of VBs decreased, the aggregation and acidic species increased significantly. Thus, our observations highlight the importance of setting an additional annealing step with a suitable temperature, which contributes to reducing the VBs while maintaining the stability of the high concentration freeze-dried protein formulation | ||
| 650 | 4 | |a Journal Article | |
| 650 | 4 | |a freeze-drying | |
| 650 | 4 | |a high concentration monoclonal antibody formulation | |
| 650 | 4 | |a omalizumab | |
| 650 | 4 | |a reconstitution | |
| 650 | 4 | |a stability | |
| 650 | 4 | |a visible bubble | |
| 650 | 7 | |a Omalizumab |2 NLM | |
| 650 | 7 | |a 2P471X1Z11 |2 NLM | |
| 650 | 7 | |a Proteins |2 NLM | |
| 700 | 1 | |a Ge, Xin-Zhe |e verfasserin |4 aut | |
| 700 | 1 | |a Liu, Jia-Wei |e verfasserin |4 aut | |
| 700 | 1 | |a Wang, Si-Tao |e verfasserin |4 aut | |
| 700 | 1 | |a Xu, Jie |e verfasserin |4 aut | |
| 700 | 1 | |a Fang, Wei-Jie |e verfasserin |4 aut | |
| 773 | 0 | 8 | |i Enthalten in |t Molecular pharmaceutics |d 2004 |g 21(2024), 4 vom: 01. Apr., Seite 1691-1704 |w (DE-627)NLM154556807 |x 1543-8392 |7 nnns |
| 773 | 1 | 8 | |g volume:21 |g year:2024 |g number:4 |g day:01 |g month:04 |g pages:1691-1704 |
| 856 | 4 | 0 | |u http://dx.doi.org/10.1021/acs.molpharmaceut.3c00991 |3 Volltext |
| 912 | |a GBV_USEFLAG_A | ||
| 912 | |a GBV_NLM | ||
| 951 | |a AR | ||
| 952 | |d 21 |j 2024 |e 4 |b 01 |c 04 |h 1691-1704 | ||