title: Novel NSAIDs ophthalmic formulation: flurbiprofen axetil emulsion with low irritancy and improved anti-inflammation effect.
abstract: The aim of this study was to design and formulate a novel low-irritant NSAIDs ophthalmic emulsion of flurbiprofen axetil (FBA), the prodrug of flurbiprofen (FB). FBA ophthalmic emulsion (FBA-EM) was prepared by high-pressure homogenization with caster oil as oil phase and tween 80 as emulsifying agent. Results from the stability evaluation suggested the protect effect of oil droplets on the stability of FBA. Compared with FBA-oil solution, the AUC(0→10h) of FB in aqueous humor administered in FBA-EMs exhibited 6.7-fold (F2), 4.5-fold (F3) and 4.6-fold (F4) increase. With the increment of oil content, the MRT also prolonged, which of FBA-EM F2-F4 were 5.14 ± 2.23, 5.73 ± 3.35 and 8.71 ± 0.94 h, respectively. No significant difference was found between the ocular bioavailability of FBA-EM F2 and 0.03% FB-Na eye drops. Ocular irritation evaluation revealed that FBA-EM F2 had better ocular biocompatibility than 0.03% FB-Na eye drops, even though the FBA concentration was up to 0.1%. Intraocular anti-inflammation effect evaluation showed that FBA-EM F2 had a quite good anti-inflammation effect. In conclusion, FBA-EM F2 with elevated FBA concentration to be 0.1% might represent a promising NSAIDs ophthalmic emulsion with low irritancy and improved anti-inflammation effect.
authors: Shanghai Institute of Materia Medica, Chinese Academy of Sciences, 501 Haike Road, Shanghai 201203, China.
authors: Jinqiu
authors: J
authors: Shen
authors: Li
authors: L
authors: Gan
authors: Chunliu
authors: C
authors: Zhu
authors: Xinxin
authors: X
authors: Zhang
authors: Yang
authors: Y
authors: Dong
authors: Min
authors: M
authors: Jiang
authors: Jiabi
authors: J
authors: Zhu
authors: Yong
authors: Y
authors: Gan
mesh_terms: D000818:Animals; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D001082:Aqueous Humor / Q000166:cytology / Q000378:metabolism; D001682:Biological Availability; D002452:Cell Count; D003315:Cornea / Q000166:cytology / Q000187:drug effects; D015232:Dinoprostone / Q000378:metabolism; D004339:Drug Compounding; D004355:Drug Stability; D045703:Emulsifying Agents / Q000737:chemistry; D004655:Emulsions; D005480:Flurbiprofen / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use; D007962:Leukocytes; D008297:Male; D054118:Nanospheres / Q000737:chemistry; D009883:Ophthalmic Solutions; D010316:Particle Size; D014677:Pharmaceutical Vehicles / Q000737:chemistry; D011355:Prodrugs / Q000009:adverse effects* / Q000378:metabolism / Q000493:pharmacokinetics / Q000627:therapeutic use*; D011817:Rabbits; D013696:Temperature; D014605:Uveitis / Q000188:drug therapy / Q000473:pathology
chemical_list: D000894:Anti-Inflammatory Agents, Non-Steroidal; D045703:Emulsifying Agents; D004655:Emulsions; D009883:Ophthalmic Solutions; D014677:Pharmaceutical Vehicles; D011355:Prodrugs; D005480:Flurbiprofen; C504422:flurbiprofen axetil; D015232:Dinoprostone