Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies  

作　　者：Zhining Ma Yuequan Wang Huiyang He Tong Liu Qikun Jiang Xiaohong Hou 

机构地区：[1]School of Pharmacy,Shenyang Pharmaceutical University,Shenyang 110016,China [2]Wuya College of Innovation,Shenyang Pharmaceutical University,Shenyang 110016,China [3]Liaoning Provincial Institute of Drug Inspection and Testing,Shenyang 110036,China [4]School of Pharmaceutical Engineering,Shenyang Pharmaceutical University,Shenyang 110016,China

出　　处：《Asian Journal of Pharmaceutical Sciences》2024年第3期177-189,共13页亚洲药物制剂科学（英文）

基　　金：financially supported by the National Postdoctoral Foundation of China(No.2023M730375);Liaoning Province Department of Education Project(No.LJKMZ20221365);the State Key Laboratory of Natural and Biomimetic Drugs(No.K202215)。

摘　　要：Flurbiprofen(FB),a nonsteroidal anti-inflammatory drug,is widely employed in treating ocular inflammation owing to its remarkable anti-inflammatory effects.However,the racemic nature of its commercially available formulation(Ocufen^(R))limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired antiinflammatory effects.Additionally,the limited corneal permeability of FB significantly restricts its bioavailability.In this study,we successfully separated the chiral isomers of FB to obtain the highly active(S)-FB.Subsequently,utilizing ion-pairing technology,we coupled(S)-FB with various counter-ions,such as sodium,diethylamine,trimethamine(TMA),and l-arginine,to enhance its ocular bioavailability.A comprehensive evaluation encompassed balanced solubility,octanol-water partition coefficient,corneal permeability,ocular pharmacokinetics,tissue distribution,and in vivo ocular anti-inflammatory activity of each chiral isomer salt.Among the various formulations,S-FBTMA exhibited superior water solubility(about 1–12 mg/ml),lipid solubility(1<lgP_(ow)<3)and corneal permeability.In comparison to Ocufen^(R),S-FBTMA demonstrated significantly higher in vivo antiinflammatory activity and lower ocular irritability(such as conjunctival congestion and tingling).The findings from this research highlight the potential of chiral separation and ion-pair enhanced permeation techniques in providing pharmaceutical enterprises focused on drug development with a valuable avenue for improving therapeutic outcomes.

关 键 词：FLURBIPROFEN ANTI-INFLAMMATORY Ophthalmic delivery Chiral resolution ION-PAIRING 

分 类 号：R943[医药卫生—药剂学]