From pills to sprays: rethinking antiemetics in pregnancy

Mathura Thirugnanasampanthar¹, Haonan Zhang¹, Diala Dabbar¹, Melanie Nana^2,3 & Ben Forbes¹

¹Institute of Pharmaceutical Sciences, King’s College London, London, SE1 9NH, UK

²Department of Women and Children’s Health, King’s College London, London, SE1 9NH, UK

³Guy’s and St Thomas’ NHS Foundation Trust, London, SE1 7EH, UK

Summary

Nausea and vomiting in pregnancy (NVP) and the severe form of the disease, hyperemesis gravidarum (HG), affect up to 90% and 3.6% of pregnant individuals, respectively. Ondansetron, approved for medical use in 1990, is a widely prescribed treatment for managing nausea and vomiting associated with chemotherapy, radiotherapy, and surgery, but is also used off-label to treat NVP and HG. Ondansetron is available for oral, intravenous, and intramuscular administration. Intravenous delivery is invasive, with poor drug penetration across the blood-brain barrier and reduced access to central receptors. Oral administration undergoes hepatic first-pass metabolism, reducing its bioavailability. A nasal spray formulation of ondansetron offers a promising alternative that addresses the challenges of oral and intravenous administration and may fulfil the need for an effective, non-off-label treatment option for NVP and HG. This work presents early patient engagement work, formulation studies, and analysis of regional deposition in a nasal cast for a nasal spray formulation of ondansetron intended for the treatment of pregnancy-related nausea and vomiting.