Purpose: To probe the suitability of a dry-powder oxytocin formulation containing a carrier (μco™; SNBL, Ltd.) for intranasal (IN) administration to treat post-partum hemorrhage in the developing world. Specifically, to investigate (1) whether IN administration can achieve rapid systemic absorption in cynomolgus monkeys, and (2) whether the formulation exhibits sufficient physical and chemical stability. This study was conducted to support Merck for Mothers, Merck's 10-year global initiative to end preventable maternal deaths.
Methods: A partial-crossover pharmacokinetic (PK) study in cynomolgus monkeys (n = 6) was utilized to compare in vivo absorption of dry-powder IN oxytocin at three dose levels against an IM injection of an aqueous oxytocin formulation. Particle size distribution, delivered dose and chemical assay were monitored over a 12 month stability study.
Results: IN administration of oxytocin resulted in short (5 min) Tmax and good dose linearity in AUC and Cmax over the dose range tested (10-80 IU per animal). The relative bioavailability (BA) of IN oxytocin to IM injection was approximately 12%. The 80 IU formulation exhibited good physical stability and consistent dosing. After 12 months at 30°C/65%RH, pouched samples retained 86.0% of their original assay value.
Conclusions: The PK and stability data suggests that IN administration of oxytocin formulated in the μco™ carrier may represent a viable option for rapid systemic absorption in humans and a product compatible with resource-scarce regions.
Keywords: intranasal absorption; peptide; pharmacokinetics; preclinical; stability.