Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations
Due to the growing demand for patient-friendly subcutaneous dosage forms, the ability to increasing protein solubility and stability in formulations to deliver on the required high protein concentrations is crucial. A common approach to ensure protein solubility and stability in high concentration p...
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| Format: | Article |
| Language: | English |
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MDPI AG
2022-08-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/27/16/5094 |
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| author | Tanja Stolzke Franziska Krieg Tao Peng Hailong Zhang Olaf Häusler Christoph Brandenbusch |
| author_facet | Tanja Stolzke Franziska Krieg Tao Peng Hailong Zhang Olaf Häusler Christoph Brandenbusch |
| author_sort | Tanja Stolzke |
| collection | DOAJ |
| description | Due to the growing demand for patient-friendly subcutaneous dosage forms, the ability to increasing protein solubility and stability in formulations to deliver on the required high protein concentrations is crucial. A common approach to ensure protein solubility and stability in high concentration protein formulations is the addition of excipients such as sugars, amino acids, surfactants, approved by the Food and Drug Administration. In a best-case scenario, these excipients fulfil multiple demands simultaneously, such as increasing long-term stability of the formulation, reducing protein adsorption on surfaces/interfaces, and stabilizing the protein against thermal or mechanical stress. 2-Hydroxylpropyl-β-cyclodextrin (derivative of β-cyclodextrin) holds this potential, but has not yet been sufficiently investigated for use in protein formulations. Within this work, we have systematically investigated the relevant molecular interactions to identify the potential of Kleptose<sup>®</sup>HPB (2-hydroxylpropyl-β-cyclodextrin from Roquette Freres, Lestrem, France) as “multirole” excipient within liquid protein formulations. Based on our results three factors determine the influence of Kleptose<sup>®</sup>HPB on protein formulation stability: (1) concentration of Kleptose<sup>®</sup>HPB, (2) protein type and protein concentration, and (3) quality of the protein formulation. Our results not only contribute to the understanding of the relevant interactions but also enable the target-oriented use of Kleptose<sup>®</sup>HPB within formulation design. |
| first_indexed | 2024-03-09T12:52:13Z |
| format | Article |
| id | doaj.art-b1ade49b2a8643e68da8d9e1c3c3cd80 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-09T12:52:13Z |
| publishDate | 2022-08-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-b1ade49b2a8643e68da8d9e1c3c3cd802023-11-30T22:04:12ZengMDPI AGMolecules1420-30492022-08-012716509410.3390/molecules27165094Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein FormulationsTanja Stolzke0Franziska Krieg1Tao Peng2Hailong Zhang3Olaf Häusler4Christoph Brandenbusch5Laboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, GermanyLaboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, GermanyRoquette Asia Pacific Pte. Ltd., Singapore 138588, SingaporeRoquette Asia Pacific Pte. Ltd., Singapore 138588, SingaporeRoquette Freres, 62080 Lestrem, FranceLaboratory of Thermodynamics, Department of Biochemical and Chemical Engineering, TU Dortmund University, 44227 Dortmund, GermanyDue to the growing demand for patient-friendly subcutaneous dosage forms, the ability to increasing protein solubility and stability in formulations to deliver on the required high protein concentrations is crucial. A common approach to ensure protein solubility and stability in high concentration protein formulations is the addition of excipients such as sugars, amino acids, surfactants, approved by the Food and Drug Administration. In a best-case scenario, these excipients fulfil multiple demands simultaneously, such as increasing long-term stability of the formulation, reducing protein adsorption on surfaces/interfaces, and stabilizing the protein against thermal or mechanical stress. 2-Hydroxylpropyl-β-cyclodextrin (derivative of β-cyclodextrin) holds this potential, but has not yet been sufficiently investigated for use in protein formulations. Within this work, we have systematically investigated the relevant molecular interactions to identify the potential of Kleptose<sup>®</sup>HPB (2-hydroxylpropyl-β-cyclodextrin from Roquette Freres, Lestrem, France) as “multirole” excipient within liquid protein formulations. Based on our results three factors determine the influence of Kleptose<sup>®</sup>HPB on protein formulation stability: (1) concentration of Kleptose<sup>®</sup>HPB, (2) protein type and protein concentration, and (3) quality of the protein formulation. Our results not only contribute to the understanding of the relevant interactions but also enable the target-oriented use of Kleptose<sup>®</sup>HPB within formulation design.https://www.mdpi.com/1420-3049/27/16/50942-hydroxylpropyl-β-cyclodextrinKleptose<sup>®</sup>HPBauto-associationmonoclonal antibodyprotein stabilitysurface tension |
| spellingShingle | Tanja Stolzke Franziska Krieg Tao Peng Hailong Zhang Olaf Häusler Christoph Brandenbusch Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations Molecules 2-hydroxylpropyl-β-cyclodextrin Kleptose<sup>®</sup>HPB auto-association monoclonal antibody protein stability surface tension |
| title | Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations |
| title_full | Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations |
| title_fullStr | Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations |
| title_full_unstemmed | Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations |
| title_short | Hydroxylpropyl-β-cyclodextrin as Potential Excipient to Prevent Stress-Induced Aggregation in Liquid Protein Formulations |
| title_sort | hydroxylpropyl β cyclodextrin as potential excipient to prevent stress induced aggregation in liquid protein formulations |
| topic | 2-hydroxylpropyl-β-cyclodextrin Kleptose<sup>®</sup>HPB auto-association monoclonal antibody protein stability surface tension |
| url | https://www.mdpi.com/1420-3049/27/16/5094 |
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