Thermal stability study of aqueous oxytocin formulation for intranasal delivery

摘要

Post-partum haemorrhage has been highlighted as one of the most common causes of maternal deaths in third world countries. Oxytocin, a pharmaceutical neuropeptide, was identified as the drug of first choice to treat post-partum haemorrhage. It is currently available in the form of intravenous administration and requires cold-chain supply and storage condition as oxytocin degrades rapidly at 30 oC and above. Most third world countries experience tropical climate where temperature frequently hovers above 30 oC. Cold-chain supply and storage are often inadequate in these places. Additionally, in rural areas, most women give birth at home and intravenous injection requires skilled medical personnel to administer which are often not immediately available. In the present studies, intranasal delivery of oxytocin in aqueous micellar formulation is explored. Intranasal delivery of oxytocin eliminates the requirement of medical personnel to perform the injection. Furthermore, the neuroepithelium in the olfactory region of the nasal cavity facilitates the delivery of brain drug through the central nervous system, making intranasal delivery of oxytocin the preferred route of administration. Here, we developed surfactant micellar formulations using Tween 80, Cremophor RH40 and sucrose laurate for intranasal delivery of oxytocin in aqueous medium. Thermal stability of these formulations was evaluated and micellar formulation with sucrose laurate demonstrated enhanced stability of oxytocin at storage temperature of 40 oC while those with Tween 80 and Cremophor RH40 adversely affected the thermal stability of oxytocin. Addition of a mucoadhesive, carboxylmethylcellulose, also negatively influenced the thermal stability of oxytocin in aqueous formulations.