The hormone oxytocin is given as standard during the third stage of labour to induce childbirth but the need for sterility and its reaction to temperature change means administration by injection in the developing world is an issue, according to GlaxoSmithKline Investigator and expert in inhalation delivery of biopharmaceuticals Richard Kaye.
He told a packed room at the annual AAPS meeting in San Diego yesterday an inhalable form of the peptide had the ability to prevent 41 million post-partum haemorrhages (PPHs) and over two million deaths in developing countries over a ten year period, and the Big Pharma company is working with Australia’s Monash University to achieve this.
“We are combining GSK’s infrastructure with Monash’s concept in order to expedite the development of this peptide,” he said. “The product will utilise our DPI [dry powder inhaler] manufacturing platforms to make a single-dose therapy, a throwaway device, which is essentially cheap as the governments and patients don’t have much to spend, and is stable at 30⁰C.”
The device which is being investigated is GSK’s Rotahaler which can be produced for under 10 pence (16 cents) per unit and can quickly deliver approximately 30mg of product.
Formulation Challenges
Using the lungs for systematic delivery of peptides and large molecule is not new exactly, as this has been achieved in the past with inhalable insulins - the US FDA recently approved Mannkind’s Afrezza for example. The technology challenge comes when formulating the drug to ensure a cost effective amount of the large molecule API is efficiently administered into the lungs, Kaye said.
“We procure the API as a freeze dried powder, dissolve it, add excipients with spray drying, and blend it with our carrier particle,” he said.
The role of the excipients helps to increase the solubility of the peptide and allows rapid clearance from the lungs. A carbohydrate is used as a water replacer and glassy stabiliser in spray-dried formulation, Kaye said, while an unnamed formulation additive helps improve stability.
Usually GSK uses lactose as the carrier in inhaled formulations but due to the nature of the oxytocin molecule the firm is using an alternative in this project.