Innovative strategies for stabilization of therapeutic peptides in aqueous formulations

PhD ceremony: Ms. C. Avanti, 16.15 uur, Academiegebouw, Broerstraat 5, Groningen

Dissertation: Innovative strategies for stabilization of therapeutic peptides in aqueous formulations

Promotor(s): prof. H.W. Frijlink

Faculty: Mathematics and Natural Sciences

Every year 166 000 women die of bleeding after child birth, and more than 50% of these deaths occur in sub-Saharan Africa (Clyburn et. al., 2007). Oxytocin, a nonapeptide which is the drug of first choice to treat bleeding after childbirth or post-partum hemorrhage (PPH). Although the availability of this drug has greatly declined maternal mortality rates in the developed world, PPH remains a leading cause of maternal mortality elsewhere. Current commercial formulations of oxytocin are insufficiently heat-stable to withstand tropical conditions.

The starting point for the research of Christina Avanti was the insufficient access of mothers in the tropical developing countries to liquid oxytocin formulations for injection which are heat stable, affordable, and simple to use. In her research she has been able to find oxytocin formulations with an improved stablility. These formulations are based on combinations of divalent cations (calcium, zinc or magnesium) and carboxylate buffers (e.g. citrate, malonate or aspartate). Furthermore the degradation pathways of oxytocin were investigated and further understanding of the mechanism by which the cations and buffers stabilize the oxytocin was gained.