Recombinant human granulocyte colony stimulating factor pre-screening and screening of stabilizing carbohydrates and polyols

Pavisic, Renata, Hock, Karlo, Mijic, Ivana, Horvatic, Anita, Gecan, Martina, Sedic, Mirela, Bukvic Krajacic, Mirjana and Cindric, Mario (2010) Recombinant human granulocyte colony stimulating factor pre-screening and screening of stabilizing carbohydrates and polyols. International Journal of Pharmaceutics, 387 1-2: 110-119. doi:10.1016/j.ijpharm.2009.12.015


Author Pavisic, Renata
Hock, Karlo
Mijic, Ivana
Horvatic, Anita
Gecan, Martina
Sedic, Mirela
Bukvic Krajacic, Mirjana
Cindric, Mario
Title Recombinant human granulocyte colony stimulating factor pre-screening and screening of stabilizing carbohydrates and polyols
Journal name International Journal of Pharmaceutics   Check publisher's open access policy
ISSN 0378-5173
1873-3476
Publication date 2010
Sub-type Article (original research)
DOI 10.1016/j.ijpharm.2009.12.015
Open Access Status
Volume 387
Issue 1-2
Start page 110
End page 119
Total pages 10
Place of publication Amsterdam, Netherlands
Publisher Elsevier
Language eng
Subject 3003 Pharmaceutical Science
Abstract Protein stabilization by solvent additives is frequently used concept in formulation development, although new technologies implemented over the past decade can improve protein biophysical as well as clinical properties by protein structural design (e.g. PEGylation, acylation, hesylation). The scope of this work was to evaluate the effect of chosen carbohydrate or polyol stabilizer in the formulation; firstly on linear peptide sequences on instable model of r. HuG-CSF cleaved macromolecule by novel method named protein and peptide stabilizer pre-screening PPSP (formulated tryptic digest mixture stability evaluation in 54. h) and on overall stability of r. HuG-CSF macromolecule by quantifying all relevant degradation parameters. Comprehensive protein stabilizing screening study included conformational analysis of formulated r. HuG-CSF protein to obtain information on its secondary structure conformational stability. Protein aggregation induced by modulating conditions in solution (e.g. thermal stress and agitation) was monitored over discrete time periods. Oxidation and deamidation, as well as truncation or hydrolysis were accurately quantified. Together with pre-screening data, obtained by fast and resourceful amino acid sequence degradation analysis by LC-MS, statistical data evaluation of stabilizing contribution of substances selected from group of carbohydrates and polyols was performed. According to the statistical interpretation of obtained results the stabilizers were ranked in the following order: turanose, d-trehalose, lactitol, acetate buffer (non-stabilized sample), xylitol, cellobiitol, sorbitol, d-lyxose, leucrose, sorbitol without polysorbate, cellobiose.
Keyword Formulation
Protein and peptide
RHuG-CSF
Screening
Stabilizer
Q-Index Code C1
Q-Index Status Provisional Code
Institutional Status Non-UQ

Document type: Journal Article
Sub-type: Article (original research)
Collection: School of Biological Sciences Publications
 
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Created: Wed, 27 Aug 2014, 14:22:02 EST by Gail Walter on behalf of School of Biological Sciences