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 form...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.展开更多
针对烟酸注射液含量和有关物质建立反相高效液相色谱法(RP-HPLC)含量测定方法。方法 RP-HPLC测定方法采用GL AQ C18色谱柱(250mm×4.6mm,5µm),流动相:0.05mol/L磷酸二氢钠溶液-甲醇(98:2),梯度洗脱。流速:1.0ml/min,检测波长:2...针对烟酸注射液含量和有关物质建立反相高效液相色谱法(RP-HPLC)含量测定方法。方法 RP-HPLC测定方法采用GL AQ C18色谱柱(250mm×4.6mm,5µm),流动相:0.05mol/L磷酸二氢钠溶液-甲醇(98:2),梯度洗脱。流速:1.0ml/min,检测波长:261nm,柱温:35.0℃,进样量:20µl。结果 烟酸在0.002004~0.05010mg/ml的浓度范围线性良好,相关系数均大于0.999,使用RP-HPLC法,可顺利检出烟酸注射液的有关物质。结论 本研究建立RP-HPLC法能准确测定烟酸注射液的含量和有关物质,方法简洁、可靠,可用于烟酸注射液的含量测定和质量控制。展开更多
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)。
文摘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.
