Ketoroloac tromethamine loaded nanodispersion incorporated into thermosensitive in situ gel for prolonged ocular delivery

Int J Pharm. 2016 Jun 15;506(1-2):57-67. doi: 10.1016/j.ijpharm.2016.04.021. Epub 2016 Apr 26.

Abstract

The present study was designed to improve the ocular availability of ketorolac tromethamine and to prolong its precorneal residence time for the treatment of postoperative ocular inflammation. Ketorolac tromethamine nanodispersions were successfully prepared by nanoprecipitation method using Eudragit(®) RL100. These nanodispersions were characterized in terms of particle size, zeta potential, entrapment efficiency and in vitro release. Consequently, the optimum nanodispersion was incorporated into thermosensitive in situ gel. The optimum gelling capacity was obtained by 20% Pluronic(®) F-127 and 14% Pluronic(®) F-127/1.5% HPMC K4m. The gelling temperature and gelation time of the in situ gels increased by decreasing the concentration of Pluronic(®) F-127. The mucoadhesive strength was significantly improved by the addition of HPMC. Incorporation of ketorolac tromethamine loaded nanodispersions into in situ gel bases sustained the release of ketorolac tromethamine, improved its ocular availability and prolonged its residence time without causing irritation to eye.

Keywords: Eudragit RL100 nanoparticles; In situ gel; Nanoprecipitation method; Ocular availability; Ocular retention; Pluronics.

MeSH terms

  • Animals
  • Biological Availability
  • Chemistry, Pharmaceutical / methods
  • Delayed-Action Preparations / administration & dosage
  • Delayed-Action Preparations / chemistry*
  • Delayed-Action Preparations / metabolism
  • Drug Carriers / chemistry
  • Drug Delivery Systems / methods
  • Eye / drug effects*
  • Gels / administration & dosage*
  • Gels / chemistry*
  • Gels / metabolism
  • Ketorolac Tromethamine / administration & dosage*
  • Ketorolac Tromethamine / chemistry*
  • Ketorolac Tromethamine / metabolism
  • Lactose / analogs & derivatives
  • Lactose / chemistry
  • Methylcellulose / analogs & derivatives
  • Methylcellulose / chemistry
  • Nanoparticles / administration & dosage
  • Nanoparticles / chemistry*
  • Particle Size
  • Poloxamer / chemistry
  • Rabbits
  • Temperature

Substances

  • Delayed-Action Preparations
  • Drug Carriers
  • Gels
  • hydroxypropylmethylcellulose-lactose matrix
  • Poloxamer
  • Ketorolac Tromethamine
  • Methylcellulose
  • Lactose