Microcapsule-gel formulation of promethazine HCl for controlled nasal delivery:A motion sickness medication

摘要

The current method of choice for astronauts to treat space motion sickness is an intra-muscular injection of promethazine hydrochloride (PMZ HCl) which is invasive and causes considerable local irritation and discomfort at the site of injection.Intra-nasal delivery is considered a feasible alternative route for administration of medications to treat space motion sickness.The purpose of this research is to develop a PMZ HCl formulation that can be administered intra-nasally without irritation (i.e.leukocyte infiltration) in the nasal epithelium when dosed at PMZ HCl concentrations greater than the cytotoxic limit.The biocompatibility of PMZ HCl was tested in vitro and was shown to be cytotoxic at concentrations greater than 10~(-5) molar regardless of pH.A controlled-release microencapsulated dosage formulation was developed using spinning disk atomization and release rates for the PMZ HCl microcapsules were determined in phosphate buffered saline.An animal study was conducted to determine the irritation response of rat nasal mucosa when dosed with encapsulated and non-encapsulated PMZ HCl.