Protein-excipient interactions evaluated via NMR studies in polysorbate based multi-dose protein formulations: influence on antimicrobial efficacy and potential study approach
Protein-excipient interactions evaluated via NMR studies in polysorbate based multi-dose protein formulations: influence on antimicrobial efficacy and potential study approach
Publication date: Available online 5 June 2018 Source:Journal of Pharmaceutical Sciences
Author(s): Riccardo Torosantucci, Britta Furtmann, Bettina Elshorst, Stefania Pfeiffer-Marek, Tanja Hartleb, Nikolaus Andres, Till Bussemer
Preservatives are excipients essentially needed in pharmaceutical multi-dose formulations to prevent microbial growth. Among available substances, phenol is widely used for parenterals, however, it is known to interact with non-ionic surfactants like polysorbate and potentially with the active pharmaceutical ingredient. Although the need for combinations of surfactants and preservatives is growing, to date possible molecular interactions which can eventually weaken the stability and antimicrobial activity of the formulation are not yet well understood and properly investigated. In the current study, the binding of phenol to a model fusion protein as well as to polysorbate 20 was investigated. For this purpose, the fraction of bound phenol was successfully quantified via diffusion ordered NMR spectroscopy. The binding of phenol to the surfactant is negligible in pharmaceutically relevant polysorbate concentrations, but the binding to the employed active pharmaceutical ingredient was relevant and concentration dependent. The resulting consequence of this interaction was the decrease of the antimicrobial efficacy. As a final outcome of this study, NMR analysis is proposed as a material saving method to be used in combination with the antimicrobial activity testing described in the Pharmacopoeias.
[NMR paper] Emulsifying properties development of pork myofibrillar and sacroplasmic protein irradiated at different dose: A combined FT-IR spectroscopy and low-field NMR study.
Emulsifying properties development of pork myofibrillar and sacroplasmic protein irradiated at different dose: A combined FT-IR spectroscopy and low-field NMR study.
Emulsifying properties development of pork myofibrillar and sacroplasmic protein irradiated at different dose: A combined FT-IR spectroscopy and low-field NMR study.
Food Chem. 2018 Jun 30;252:108-114
Authors: Li C, Peng A, He L, Ma S, Wu W, Yang H, Sun X, Zeng Q, Jin G, Zhang J, Ma M
Abstract
The present study investigated the effect of different irradiation dose...
nmrlearner
Journal club
0
02-27-2018 12:30 PM
Emulsifying properties development of pork myofibrillar and sacroplasmic protein irradiated at different dose: A combined FT-IR spectroscopy and low-field NMR study
Emulsifying properties development of pork myofibrillar and sacroplasmic protein irradiated at different dose: A combined FT-IR spectroscopy and low-field NMR study
Publication date: 30 June 2018
Source:Food Chemistry, Volume 252</br>
Author(s): Chengliang Li, An Peng, Lichao He, Sumin Ma, Wenmin Wu, Haiyan Yang, Xiuxiu Sun, Qi Zeng, Guofeng Jin, Jianhao Zhang, Meihu Ma</br>
The present study investigated the effect of different irradiation dose (0, 3, 5 and 7 kGy) on the emulsifying properties development of pork myofibrillar protein (MP) and...
nmrlearner
Journal club
0
02-03-2018 02:16 PM
[NMR paper] Effect of Polysorbate 20 and Polysorbate 80 on the Higher Order Structure of a Monoclonal Antibody and its Fab and Fc Fragments Probed Using 2D NMR.
Effect of Polysorbate 20 and Polysorbate 80 on the Higher Order Structure of a Monoclonal Antibody and its Fab and Fc Fragments Probed Using 2D NMR.
Effect of Polysorbate 20 and Polysorbate 80 on the Higher Order Structure of a Monoclonal Antibody and its Fab and Fc Fragments Probed Using 2D NMR.
J Pharm Sci. 2017 Aug 23;:
Authors: Singh SM, Bandi S, Jones DNM, Mallela KMG
Abstract
We examined how polysorbate 20 (PS20; Tween 20) and polysorbate 80 (PS80; Tween 80) affect the higher order structure of a monoclonal antibody (mAb)...
nmrlearner
Journal club
0
08-28-2017 10:59 AM
[NMR paper] Cu(II)-Based Paramagnetic Probe to Study RNA-Protein Interactions by NMR.
Cu(II)-Based Paramagnetic Probe to Study RNA-Protein Interactions by NMR.
Related Articles Cu(II)-Based Paramagnetic Probe to Study RNA-Protein Interactions by NMR.
Inorg Chem. 2017 Mar 22;
Authors: Seebald LM, DeMott CM, Ranganathan S, Asare Okai PN, Glazunova A, Chen A, Shekhtman A, Royzen M
Abstract
Paramagnetic NMR techniques allow for studying three-dimensional structures of RNA-protein complexes. In particular, paramagnetic relaxation enhancement (PRE) data can provide valuable information about long-range distances between...
nmrlearner
Journal club
0
03-23-2017 08:51 PM
[NMR paper] Structure-based drug design: NMR-based approach for ligand-protein interactions.
Structure-based drug design: NMR-based approach for ligand-protein interactions.
Related Articles Structure-based drug design: NMR-based approach for ligand-protein interactions.
Drug Discov Today Technol. 2006;3(3):241-5
Authors: Zhang X, Tang H, Ye C, Liu M
Abstract
The realization of the powerfulness in analyzing ligand-protein interactions at the atomic resolution has made NMR techniques increasingly attractive in drug discovery and development. With some significant new method developments during the past few years,...
nmrlearner
Journal club
0
07-06-2014 08:28 PM
[NMR paper] NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1 AM treatment.
NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1 AM treatment.
Related Articles NMR-based metabolomics and breath studies show lipid and protein catabolism during low dose chronic T1 AM treatment.
Obesity (Silver Spring). 2013 Mar 20;
Authors: Haviland JA, Reiland H, Butz DE, Tonelli M, Porter WP, Zucchi R, Scanlan TS, Chiellini G, Assadi-Porter FM
Abstract
OBJECTIVE: 3-iodothyronamine (T1 AM), an analog of thyroid hormone,is a recently discovered fast-acting endogenous metabolite. High...
nmrlearner
Journal club
0
03-21-2013 02:58 PM
[NMR paper] Using a Fragment-Based Approach To Target Protein-Protein Interactions.
Using a Fragment-Based Approach To Target Protein-Protein Interactions.
http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2250-98-WileyOnlineLibrary-Button_120x27px_FullText.gif http://www.ncbi.nlm.nih.gov/corehtml/query/egifs/http:--media.wiley.com-assets-2251-04-WileyOnlineLibrary-Button_120x27px_FullTextFree.gif Related Articles Using a Fragment-Based Approach To Target Protein-Protein Interactions.
Chembiochem. 2013 Jan 23;
Authors: Scott DE, Ehebauer MT, Pukala T, Marsh M, Blundell TL, Venkitaraman AR, Abell C, Hyvönen M
...
nmrlearner
Journal club
0
02-03-2013 10:19 AM
[NMR paper] Protein-water interactions from 2H NMR relaxation studies: influence of hydrophilic,
Protein-water interactions from 2H NMR relaxation studies: influence of hydrophilic, hydrophobic, and electrostatic interactions.
Related Articles Protein-water interactions from 2H NMR relaxation studies: influence of hydrophilic, hydrophobic, and electrostatic interactions.
Adv Exp Med Biol. 1991;302:541-60
Authors: Kumosinski TF, Pessen H, Farrell HM
The importance of water interactions with proteins in food systems is well documented. A controversy exists, however, as to the nature of these interactions and the effect of protein structural...
Protein-excipient interactions evaluated via NMR studies in polysorbate based multi-dose protein formulations: influence on antimicrobial efficacy and potential study approach
Linear Mode
