Development of Microemulsion Formulation for the Solubility  Enhancement of Flunarizine

By Surjyanarayan Mandal, Snigdha Das Mandal, Naazneen Surti, Vandana B. Patel



Abstract

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

 

Key Words : Flunarizine; Microemulsion; Solubility; Zeta potential; Pseudo-ternary phase diagrams.

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