IPEC e-newsletter - Excipients Insight June/July 2017 - 10-07-17


Inside this issue


Spore-inspired excipients could improve antibody formulations

Researchers from Cambridge University in the UK and AstraZeneca's Medimmune subsidiary have come up with an ingenious approach to improving the formulation of antibody drugs – the spore-forming behaviour of some bacterial species.

Bacterial spores are rich in a substance called pyridine-2,6-dicarboxylic acid (dipicolinic acid or DPA), in fact it accounts for around 10%-15% of spores by weight, and it seems to be intimately involved in keeping the structures stable while dormant.

"Considerable effort has been made in recent years to identify and develop new excipients that mitigate the physical and chemical instability of biological drugs," write the scientists in the International Journal of Pharmaceutics.

"Given the apparent protective role of DPA in spores, we conjectured whether it would be able to fulfil a similar function as an excipient to pharmaceutical proteins of interest."  At the moment excipients, such as arginine hydrochloride (Arg), are added to biopharmaceutical drugs in order to supress aggregation, minimise phase separation, reduce viscosity and increase shelf life.

The researchers used DPA and a quinolinic acid analogue seemed to be more effective than Arg in stabilising antibodies in liquids, as measured by reductions in the viscosity of formulations and preventing unwanted phase separation - the separation of solutions into dense (protein-rich) and diluted (protein-lean) phases.

"This work introduces a new class of organic acids − inspired by their association with bacterial spores − as novel excipients in the context of protein formulation," they conclude. "While precise mechanisms of action remain to be identified, our preliminary data suggest that these DPA salts are worthy of further investigation as novel ionic excipient for biologics formulation."




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