Development of a novel approach to enhance the solubility of ftibamzone formulation.

Abstract

Ftibamzone (FBZ) is known to be effective against herpes simplex virus that causes genital herpes but poor solubility of FBZ has reduced its therapeutic efficacy. We investigated water-soluble complexes of various nanoparticles with FBZ to improve its solubility as well as increase its absorption. Using phase-solubility technique, we measured formation constant (K_1:1 and K_1:2) values at room temperature in pH 7 buffer. Solubility was determined by dissolving FBZ or FBZ-entrapped nanoparticles in phosphate buffers and pH adjusted to different pH range (2-12). The solutions were then equilibrated for 24 hours and then filtered and analyzed using HPCL. Nanoparticles were formulated using nanoprecipitation technique and cellular uptake of nanoparticle was determined by confocal microscope. No significant FBZ solubility was observed from pH 2 to 10 however we did notice a rapid increase in solubility from pH of 10 to 12 with FBZ solubility of 950 μg/ml. Our log D against pH profile revealed that FBZ is characteristic of an acid drug since unionized group was dominant at low pH. FBZ interaction with methyl-β-cyclodextrin (mβCD) complexation/nanoparticles showed a greater solubility of FBZ compared with FBZ alone while complexation constants were determined to be K_1:1 and K_1:2 were 7.06×10^-3 and 8.98×10^-8 mM^-1 respectively. Only FBZ-chitosan nanoparticles were toxic against MDCK cells. Study demonstrates that FBZ-PLGA nanoparticles could significantly enhance the solubility and absorption of FBZ compared with FBZ alone and has the potential to be used as an effective delivery system for the treatment of genital herpes.