Heat-stable sublingual oxytocin tablets as a potential needle-free approach for preventing postpartum hemorrhage in low-resource settings.

ABSTRACT: Postpartum hemorrhage is a major cause of mortality and morbidity related to childbirth in developing countries. The recommended treatment includes administration of oxytocin; however, oxytocin is a heat-labile protein, and it must be given as an intramuscular injection by skilled health care providers. To address these challenges, we developed a freeze-dried oxytocin fast-dissolving tablet (FDT) for sublingual (SL) needle-free administration. Using methods developed previously, we produced a robust FDT that maintained oxytocin stability at 40 °C, 75% relative humidity for 12 months. This formulation contains 9% sucrose, 1.5% (hydroxypropyl)methyl cellulose, 9% mannitol, 4% dextran, 1% carbomer, 1% sodium taurocholate, and 100 IU oxytocin. An in vitro study showed a >?30% reduction in tissue transepithelial electrical resistance after treatment with the oxytocin FDT, implying an increase in the permeability of the mucosal tissue to oxytocin. Anesthetized Yucatan miniature swine were administered a SL FDT, and blood was periodically collected for a pharmacokinetic study. Higher plasma concentrations were seen when larger SL doses were given. The maximum concentrations for SL and intramuscular doses in anesthetized pigs were 207 and 612 pg/mL, respectively. Whether the levels attained will be sufficient to elicit beneficial results in humans is yet to be determined. This study demonstrates the feasibility of our approach for developing a heat-stable oxytocin tablet that can be administered successfully via the SL route.

SUBMITTER: Zhu C 

PROVIDER: S-EPMC5937893 | biostudies-other | 2018 Jun

REPOSITORIES: biostudies-other