title: Eudragit RL 100-based nanoparticulate system of aceclofenac for ocular delivery.
abstract: The purpose of this study was to prepare Eudragit RL 100-based nanoparticles of aceclofenac by nanoprecipitation and evaluate the particle size, zeta potential, drug entrapment, particle morphology; in vitro drug release and in vivo efficacy. Change in drug-polymer ratio from 1:5 to 1:20 increased the particle size and entrapment efficiency. The particles showed sustained in vitro drug release which followed the Higuchi square-root kinetics. The results indicate that the nanoparticles release the drug by a combination of dissolution and diffusion. Based on the particle size (134.97 nm) and entrapment efficiency (95.73%), the formulation made with 1:10 drug-polymer ratio was selected for further studies. The particles were spherical with a polydispersity index of 0.186 and zeta potential of +30.5 mV. Powder X-ray diffraction and differential scanning calorimetry indicated decrease in crystallinity of drug in the nanoparticle formulation. In the in vitro permeation study, the nanoparticle formulation showed 2-fold higher permeation of drug through excised cornea compared to an aqueous solution of drug with no signs of corneal damage. The in vivo studies involving arachidonic acid-induced ocular inflammation in rabbits revealed significantly higher inhibition of polymorphonuclear leukocytes migration (p<0.05) and lid closure scores by the nanoparticle formulation compared with the aqueous solution. The formulation was quite stable to ensure two year shelf life at room temperature.
authors.affiliation: Department of Pharmaceutics, Delhi Institute of Pharmaceutical Sciences and Research, Formerly College of Pharmacy, University of Delhi, Pushp Vihar, Sector III, New Delhi 110017, India.
authors.forename: Rajesh
authors.initials: R
authors.lastname: Katara
authors.forename: Dipak K
authors.initials: DK
authors.lastname: Majumdar
mesh_terms: D000180:Acrylic Resins / Q000737:chemistry*; D060433:Administration, Ophthalmic; D000818:Animals; D016718:Arachidonic Acid; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D003315:Cornea / Q000187:drug effects; D004008:Diclofenac / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000494:pharmacology; D016503:Drug Delivery Systems; D004355:Drug Stability; D005123:Eye / Q000187:drug effects*; D006041:Goats; D007249:Inflammation / Q000473:pathology; D053758:Nanoparticles / Q000737:chemistry* / Q000648:ultrastructure; D010316:Particle Size; D010539:Permeability / Q000187:drug effects; D011108:Polymers / Q000737:chemistry; D011817:Rabbits; D012996:Solutions; D017550:Spectroscopy, Fourier Transform Infrared; D055672:Static Electricity; D013499:Surface Properties; D013535:Suspensions; D014961:X-Ray Diffraction
chemical_list: D000180:Acrylic Resins; D011108:Polymers; D012996:Solutions; D013535:Suspensions; D004008:Diclofenac; D016718:Arachidonic Acid; C050528:Eudragit RS; C056498:aceclofenac