Preparation and evaluation of nanoparticles loaded ophthalmic in situ gel

Drug Deliv. 2016 Sep;23(7):2363-2370. doi: 10.3109/10717544.2014.987333. Epub 2015 Jan 12.

Abstract

Context: Conventional ophthalmic solutions often eliminate rapidly after administration and cannot provide and maintain an adequate concentration of drug in the pre-corneal area.

Objectives: Above problem can be overcome by the use of in situ gel forming systems that are instilled as drops in to the eye and undergo a sol-gel transition in the cul-de-sac.

Methods: An ion sensitive polymer gellan gum was used as gelling agent which formed immediate gel and remained for extended time period. Nanoparticles of moxifloxacin, prepared by solvent evaporation, were separated by freeze drying. The rheological properties and in vitro drug release test of in situ gel loaded with nanoparticles were evaluated and compared with marketed preparation. In vitro release study demonstrated diffusion controlled release for moxifloxacin from formulations over a period of 12 h.

Results: The developed formulation was stable and showed enhanced contact time minimizing the frequency of administration. Confocal microscopy showed clear permeation of drug loaded nanoparticles across L/S of cornea.

Conclusion: The formulation of moxifloxacin was found liquid at the formulated pH and formed gel in the presence of mono or divalent cations. The gel formed in situ showed sustained drug release over a period of 10-12 h. The formulations were less viscous before instillation and formed strong gel after instilling it into cul-de-sac. It is thus concluded that by adopting a systematic formulation approach, an optimum point can be reached in the shortest time with minimum efforts to achieve desirable rheological and in vitro release property for in situ gel forming system.

Keywords: Eudragit; gellan gum; ion sensitive in situ gel; moxifloxacin; nanoparticles.

MeSH terms

  • Cornea / chemistry
  • Cornea / metabolism*
  • Delayed-Action Preparations
  • Drug Delivery Systems / methods*
  • Fluoroquinolones / administration & dosage
  • Fluoroquinolones / chemistry*
  • Gels / chemistry*
  • Ion Transport / drug effects*
  • Moxifloxacin
  • Nanoparticles
  • Ophthalmic Solutions / chemistry*
  • Ophthalmic Solutions / pharmacology
  • Polymethacrylic Acids / chemistry
  • Polymethacrylic Acids / metabolism*
  • Polysaccharides, Bacterial / chemistry*
  • Polysaccharides, Bacterial / metabolism

Substances

  • Delayed-Action Preparations
  • Fluoroquinolones
  • Gels
  • Ophthalmic Solutions
  • Polymethacrylic Acids
  • Polysaccharides, Bacterial
  • methylmethacrylate-methacrylic acid copolymer
  • gellan gum
  • Moxifloxacin