DSC reveals the excipient impact on aggregation propensity of pharmaceutical peptides during freezing.

Abstract

Pharmaceutical peptides are susceptible to aggregation in solution, making stabilization by addition of suitable excipients essential. To investigate this stabilization, lengthy and cost-intensive experiments are often necessary. In this work, a differential scanning calorimetry (DSC) based method was developed that allows a rapid assessment of the stabilization properties of excipients regarding the aggregation of pharmaceutical peptides. The stabilization properties of investigated excipients are derived from the thermal behavior around Tg', the glass-transition temperature of the excipient-rich phase after freezing, as a function of repeated freeze-thaw cycles. The pharmaceutical peptide glucagon was investigated in combination with the excipients trehalose and lactose. In addition to the type of excipient, the concentration ratio of peptide/excipient was also varied. Lactose proved to better stabilize glucagon solutions compared to trehalose. On the one hand, the onset of aggregation could be delayed and after aggregation started the aggregation kinetics were slowed down. In addition, it was shown that a high excipient to peptide ratio, regardless of the type of excipient tested, reduces the aggregation tendency of glucagon.