Metoclopramide (MCP) can effectively alleviate motion sickness-caused nausea and vomiting. Nasal administration offers the greatest patient compliance. It is suitable for self-administration and offers rapid and complete absorption, no first-pass effects and high bioavailability. In the present study, a MCP nasal spray was prepared and evaluated in vitro and in vivo. Nasal cilia toxicity of Bufo toads was used to screen the preservative types and concentrations. Rabbit nasal mucosa was used to evaluate the mucosa permeability of different MCP nasal sprays with different penetration enhancers and preservative. A three-period crossover trial was then carried out in beagle dogs with three different MCP dosage forms: nasal sprays, oral tablets and intramuscular (IM) solution. Liquid chromatography coupled with tandem mass spectrometry (LC-MS/MS) was performed to measure dog plasma MCP, and pharmacokinetic parameters were calculated. The results of ciliatoxicity and permeation study showed that 0.03% methyl paraben lacking penetration enhancers was optimal. Compared to control IM, the bioavailability of oral tablets of MCP was 24.9%, while that of nasal spray was 62.3%. Meanwhile time-to-maximal plasma concentration (Tmax) of nasal spray was significantly shorter than that of oral tablets. In conclusion, MCP nasal spray prepared here is safe with minimal ciliatoxicity, rapid onset and high relative bioavailability.
Keywords: Metoclopramide; bioavailability; ciliatoxicity; mucosal permeability; nasal spray.