caa a22 4500 477127959 CHVBK 20180405111655.0 cr unu---uuuuu 170330e19970501xx s 000 0 eng 10.1023/A:1012101027814 doi (NATIONALLICENCE)springer-10.1023/A:1012101027814 Solvent Effects on the Solubility and Physical Stability of Human Insulin-Like Growth Factor I [Elektronische Daten] [Jonas Fransson, Dan Hallén, Ebba Florin-Robertsson] Purpose. The solubility and physical stability of human Insulin-like Growth Factor I (hIGF-I) were studied in aqueous solutions with different excipients. Methods. The solubility of hIGF-I was determined by UV-absorption and quantification of light blocking particles. The physical stability of hIGF-I was studied with differential scanning calorimetry (DSC) and circular dichroism (CD) spectroscopy. Results. Human IGF-I precipitated at low temperature in the presence of 140 mM benzyl alcohol and 145 mM sodium chloride. CD data showed that the tertiary structure of hIGF-I during these conditions was perturbed compared to that in 5 mM phosphate buffer. In the presence of benzyl alcohol 290 mM mannitol stabilized hIGF-I. Sodium chloride or mannitol by themselves had no effect on either the solubility or the tertiary structure. Benzyl alcohol was attracted to hIGF-I, whereas sodium chloride was preferentially excluded. The attraction of benzyl alcohol was reinforced by sodium chloride leading to salting-out of hIGF-I. The CD-data indicated interactions of benzyl alcohol with phenylalanine in hIGF-I. Thermal denaturation of hIGF-I occurred in all solutions with sodium chloride, whereas mannitol or benzyl alcohol had no effect on the thermal stability. The thermal stability of hlGF-I was thus decreased in 145 mM sodium chloride although it was excluded from hIGF-I. Conclusions. The self-association and thermal aggregation of hIGF-I is driven by hydrophobic interactions. Benzyl alcohol is attracted to hIGF-I and induces changes in the tertiary structure causing hydrophobic attraction of the protein at low temperatures. Plenum Publishing Corporation, 1997 hIGF-I nationallicence benzyl alcohol nationallicence preferential interaction nationallicence stability nationallicence preservative nationallicence Fransson Jonas Department of Pharmaceutical Technology, Pharmacia & Upjohn, S-, 112 87, Stockholm, Sweden aut Hallén Dan Department of Structural Chemistry, Pharmacia & Upjohn, S-l, 12 87, Stockholm, Sweden aut Florin-Robertsson Ebba Department of Pharmaceutical Technology, Pharmacia & Upjohn, S-, 112 87, Stockholm, Sweden aut Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 606-612 0724-8741 14:5<606 1997 14 11095 https://doi.org/10.1023/A:1012101027814 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1023/A:1012101027814 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Fransson Jonas Department of Pharmaceutical Technology, Pharmacia & Upjohn, S-, 112 87, Stockholm, Sweden aut NATIONALLICENCE 700 1- Hallén Dan Department of Structural Chemistry, Pharmacia & Upjohn, S-l, 12 87, Stockholm, Sweden aut NATIONALLICENCE 700 1- Florin-Robertsson Ebba Department of Pharmaceutical Technology, Pharmacia & Upjohn, S-, 112 87, Stockholm, Sweden aut NATIONALLICENCE 773 0- Pharmaceutical Research Kluwer Academic Publishers-Plenum Publishers 14/5(1997-05-01), 606-612 0724-8741 14:5<606 1997 14 11095 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer