Effect of Arginine on the Aggregation of Protein in Freeze-Dried Formulations Containing Sugars and Polyol: II. BSA Reconstitution and Aggregation
| dc.cclicence | CC-BY-NC | en |
| dc.contributor.author | Hackl, E. V. | en |
| dc.contributor.author | Darkwah, Joseph | en |
| dc.contributor.author | Smith, Geoff | en |
| dc.contributor.author | Ermolina, I. | en |
| dc.date.acceptance | 2018-06-24 | en |
| dc.date.accessioned | 2018-07-10T09:11:29Z | |
| dc.date.available | 2018-07-10T09:11:29Z | |
| dc.date.issued | 2018-07-06 | |
| dc.description | The file attached to this record is the author's final peer reviewed version. The Publisher's final version can be found by following the DOI link. | en |
| dc.description.abstract | The current paper continues our study on the ability of L-arginine to prevent/reduce the aggregation of proteins that results from the various stresses during the lyophilisation and/or storage of lyophilized protein-based products. The first part of our study, i.e. formulation development, was devoted to the rational design and optimization of an L-arginine containing lyophilized formulation which can resist the natural tendency of L-arginine to absorb atmosphere moisture. Mannitol and trehalose were chosen among other excipients to be included in the protein-based formulation, as mannitol in a combination with L-arginine has been shown to reduce moisture sorption while trehalose provides a degree of lyoprotection. In the present study, a number of formulations, which comprised bovine serum albumin (BSA) with and without L-arginine, and with five different ratios of trehalose-to-mannitol (from 30:70 to 80:20) were lyophilised and assessed. The internal structures and the moisture sorption/retention of the lyophilized formulations were characterised. To study the effect of L-arginine on BSA solid-phase stability, the lyophilized powder was exposed to accelerated storage conditions (high moisture (75% RH) and temperature (22 or 45 °C)) for up to 24 h. The lyophilized BSA formulations were then reconstituted and solution-state protein aggregation assessed by turbidimetry at 360 nm and fluorescence spectroscopy using the thioflavin T assay. It was demonstrated that L-arginine can be used in protein-based freeze-dried formulations to significantly reduce the aggregation of protein during the manufacturing, storage and subsequent reconstitution. The results also revealed the importance of a sufficient amount of mannitol in the arginine-containing formulations. | en |
| dc.funder | N/A | en |
| dc.identifier.citation | Hackl, E., Darkwah, J., Smith, G., Ermolina. I. (2018) Effect of Arginine on the Aggregation of Protein in Freeze-Dried Formulations Containing Sugars and Polyol: II. BSA Reconstitution and Aggregation, AAPS PharmSciTech, pp.1-14. | en |
| dc.identifier.doi | https://doi.org/10.1208/s12249-018-1114-0 | |
| dc.identifier.issn | 1530-9932 | |
| dc.identifier.uri | http://hdl.handle.net/2086/16330 | |
| dc.language.iso | en | en |
| dc.projectid | N/A | en |
| dc.publisher | Springer International Publishing | en |
| dc.researchgroup | Pharmaceutical Technologies | en |
| dc.researchinstitute | Leicester Institute for Pharmaceutical Innovation - From Molecules to Practice (LIPI) | en |
| dc.subject | freeze-drying | en |
| dc.subject | protein aggregation | en |
| dc.subject | L-arginine | en |
| dc.subject | mannitol | en |
| dc.subject | trehalose | en |
| dc.title | Effect of Arginine on the Aggregation of Protein in Freeze-Dried Formulations Containing Sugars and Polyol: II. BSA Reconstitution and Aggregation | en |
| dc.title.alternative | Effect of Arginine on the Protein Aggregation | en |
| dc.type | Article | en |