This research presents storage stability of human growth hormone, hGH, in a variety of lyophilized formulations, including systems of varying sugar:hGH weight ratios for both sucrose and trehalose. Stability was assessed at multiple time points during storage at 40 C and at one month at 50 C, with samples of variable water content. Large chemical and physical stability differences were observed between formulations. Tg appeared to be a relevant stability parameter only when the dried formulations were stored at temperatures near the Tg. At equivalent levels of disaccharide relative to protein, sucrose systems were twice as stable as trehalose formulations.Yet, compared to trehalose formulations, the sucrose formulations had greater structural mobility. Protein structure could not account for the difference in stability. Neutron scattering results, however, documented greater suppression of fast dynamics by sucrose than by trehalose, suggesting that well below Tg, fast dynamics are important in determining storage stability.
Citation: Journal of Pharmaceutical Sciences
Pub Type: Journals
biopharmaceutics, glassy dynamics, neutron scattering, protein stability