Objective To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes.Methods The power functions of ...Objective To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes.Methods The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived.Simulation studies were conducted to evaluate the derived power functions.Results Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed.The intra-correlation showed a positive correlation with the power of the bioequivalence test.When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval.If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power.Sample size can be calculated through numerical iteration with the derived power functions.Conclusion The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.展开更多
Topical drug administration is acommonapproach to treat ocular disorders.However,the topical route of administration enables poor drug bioavailability.These drawbacks stem from limited permeability across the cornea,r...Topical drug administration is acommonapproach to treat ocular disorders.However,the topical route of administration enables poor drug bioavailability.These drawbacks stem from limited permeability across the cornea,rapid clearance of the instilled drop,and significant absorption into the conjunctival vasculature[1].Recently,contact lens based ophthalmic drug delivery systems have been proposed as alternative ophthalmic drug delivery systems to increase ocular drug bioavailability[2].Silk fibroin,a natural fiber polymer produced by the silk worm,Bombyx mori,has excellent properties for ocular drug delivery systems,i.e.,biocompatibility,chemical and mechanical stability,wetting ability,and high oxygen permeability[3].展开更多
Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve t...Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.展开更多
基金supported by sub-project of National Major Scientific and Technological Special Project of China for ‘Significant New Drugs Development’[2015ZX09501008-004]
文摘Objective To develop methods for determining a suitable sample size for bioequivalence assessment of generic topical ophthalmic drugs using crossover design with serial sampling schemes.Methods The power functions of the Fieller-type confidence interval and the asymptotic confidence interval in crossover designs with serial-sampling data are here derived.Simulation studies were conducted to evaluate the derived power functions.Results Simulation studies show that two power functions can provide precise power estimates when normality assumptions are satisfied and yield conservative estimates of power in cases when data are log-normally distributed.The intra-correlation showed a positive correlation with the power of the bioequivalence test.When the expected ratio of the AUCs was less than or equal to 1, the power of the Fieller-type confidence interval was larger than the asymptotic confidence interval.If the expected ratio of the AUCs was larger than 1, the asymptotic confidence interval had greater power.Sample size can be calculated through numerical iteration with the derived power functions.Conclusion The Fieller-type power function and the asymptotic power function can be used to determine sample sizes of crossover trials for bioequivalence assessment of topical ophthalmic drugs.
文摘Topical drug administration is acommonapproach to treat ocular disorders.However,the topical route of administration enables poor drug bioavailability.These drawbacks stem from limited permeability across the cornea,rapid clearance of the instilled drop,and significant absorption into the conjunctival vasculature[1].Recently,contact lens based ophthalmic drug delivery systems have been proposed as alternative ophthalmic drug delivery systems to increase ocular drug bioavailability[2].Silk fibroin,a natural fiber polymer produced by the silk worm,Bombyx mori,has excellent properties for ocular drug delivery systems,i.e.,biocompatibility,chemical and mechanical stability,wetting ability,and high oxygen permeability[3].
基金special construction projects fund which belongs to“Taishan Scholar-Pharmacy Specially Recruited Experts”.
文摘Numerous systems have been designed during the past three decades to improve bioavailability of ophthalmic drug delivery,including:ocular prodrugs and nanotechnology-based drug delivery system.The former can improve the efficacy of ocular drug via enhancing corneal penetration of ocular drugs,prolonging their duration of action and/or reducing the systemic side-effects,unfortunately,some characteristics of the pro-drugs,such as poorly aqueous stability,poorly aqueous solubility and severe eye irritation probably,limit their clinical practice and cannot be ignored.As we all know,nanotech-nology for ocular drug delivery can carry poorly soluble drugs,protect the encapsulated molecules from hydrolysis,control the rate of drug delivery and prolong the precorneal retention of drugs.All of these merits may solve the problems in the utilization of ocular prodrugs and increase the bioavailability of ocular drug delivery.By reviewing recent ad-vances of prodrugs and nanostructures in ocular drug delivery,this paper focus specifically on the promising prospects of nanocarriers overcoming the drawbacks of prodrugs for ophthalmic drug delivery by precorneal routes.
