Vancomycin ocular delivery systems based on glycerol monooleate reversed hexagonal and reversed cubic liquid crystalline phases

Abstract

Lyotropic bulk reversed hexagonal and reversed cubic liquid crystalline phases (hexagonal and cubic phases) composed of glycerol monooleate (GM) were used to design the vancomycin hydrochloride’s (VHCl) delivery systems aiming to maintain VHCl’s therapeutic concentration during 24 h in the eye, locally (as an insert) and/or intravitreally (as a bulk phase injection).Bulk VHCl’s hexagonal and cubic phases were successfully prepared by melted homogenization and solvent evaporation method, and then an insert was prepared.The structural characteristics of liquid crystalline phases were studied using cross polarized light microscopy and small angle X-ray scattering technique. The presence of VHCl (1–9.5% w/w VHCl solution) did not exhibit any change in the liquid crystalline phase’s structure to another liquid crystalline phase, and showed little effect on the lattice parameter of the existing liquid crystalline phase structure.In order to relate the liquid crystalline phase structure to VHCl’s release rate locally into the eye, in-vitro release test of an implant has been done using a simulated tear fluid. VHCl’s release in the simulated tear fluid from the cubic phase obeyed Higuchi kinetics, with linear VHCl’s release versus the square root of time. The hexagonal phase released VHCl in simulated tear fluid significantly slower than the cubic phase. In order to relate the liquid phase structure to VHCl’s diffusion intravitreally, in vitro release test by the Sirius‘ Subcutaneous Injection Site Simulator (Scissor) has been performed. Comparing the release properties by a Scissor, the VHCl’s cubic phase demonstrated slower permeation through extra-cellular matrix than the VHCl solution.To evaluate the efficacy of the system investigated, the release properties of VHCl’s cubic phase were compared with literature data indicating that the cubic phase could be a potential matrix system in the delivery of VHCl intravitreally during 24 h after intravitreal injection. The release data in the simulated tear fluid indicated that the cubic phase should be further optimized to achieve a therapeutic VHCl concentration locally in the eye during 24 h.