首页|Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies
Advancing ophthalmic delivery of flurbiprofen via synergistic chiral resolution and ion-pairing strategies
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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®)limits the full potential of its therapeutic activity,as the(S)-enantiomer is responsible for the desired anti-inflammatory 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＜lg Pow＜3)and corneal permeability.In comparison to Ocufen®,S-FBTMA demonstrated significantly higher in vivo anti-inflammatory 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.
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