Development of Microemulsion Formulation for the Solubility Enhancementof Flunarizine

[摘要] Flunarizine, a piperazine derivative, is a selective Ca++ channel blocker coupled with itsantihistaminic property claimed to be effective in prophylaxis of migraine. Oral bioavailabilityof flunarizine is very low (less then 18%) due to poor water solubility and extensive first passmetabolism. The aim of the investigation was to design and develop microemulsion ofFlunarizine for enhancing its solubility hence the oral bioavailability. Solubility of flunarizinewas determined in various vehicles. Pseudo-ternary phase diagrams were constructed to identifythe microemulsion existing zone. Optimization of formulation was done by process andformulation optimization. Optimized microemulsion was characterized for its transparency,droplet size, zeta potential, viscosity, % assay, and stability study etc. Particle size and zetapotential of optimized microemulsion were found to be 12.3 nm, -6.34 mV respectively. Drugcontent of the microemulsion formulation was 98.29±0.91. The viscosity data indicated themicroemulsion to be O/W type. 78.49% and 71.53% of the drug was found to be released in 8hrsin the in-vitro and ex-vivo studies respectively. Solubility of flunarizine was successfullyenhanced by 123 times by Capmul MCM microemulsion compared with distilled water(pH=7.4). Hence, by formulating into microemulsion, the solubility of Flunarizine wassignificantly enhanced which may increase its bioavailability.

[学科分类] 药理学