Study The Release Mechanisms In Vitro And Mucosal Permeability Mechanisms On Medicine Bioadhesive Formulations-yukui Membranae

Objective: Study on the release mechanism and balanced release of the active ingredientof the traditional Chinese medicine-Yukui membranae, explore the mechanism ofbioadhesive formulations penetrate the mucosa, solve the problem of inadequatedpenetration mechanisms of bioadhesive formulations especially for complex system oftraditional Chinese medicine preparations, Institute of Chinese medicines containingbalanced release and absorption, to perfect medicine bioadhesive formulations play a role inthe mechanism, lay the foundation for further study bioadhesive formulations.Methods:(1) Through systematic research methodology to establish thedetermination of four active ingredient content of Yukui membranae,the chromatographicconditions of amphicoside Ⅰ and amphicoside Ⅱ are as follows:Agilent XDB C-18column,mathanol-water-phosphoric acid(35:65:0.1) as mobile phase with the flow rate of1mL min-1,the detection wavelength was275nm. the chromatographic conditions ofpaeonol are as follows:Agilent XDB C-18column,mathanol-water (45:55) as mobile phasewith the flow rate of1mL min-1,the detection wavelength was274nm. the chromatographicconditions of indirubin are as follows:Agilent XDB C-18column,mathanol-water (70:30) asmobile phase with the flow rate of1mL min-1,the detection wavelength was292nm. thechromatographic conditions of borneol Fused silica capillary column, flame ionizationdetector (FID), with N2as carrier gas, the temperature of the vaporization chamber250℃,column temperature140℃, separated split ratio9:1.(2).Conduct the release exprerient ofYukui membranae in water, study the drug release pattern of four kinds of index componentspicroside picroside Ⅰ and Ⅱ, paeonol, indirubin,borneol, in Yukui membranae, thecumulative release data were used to zero-order equation, an equation, Higuchi equation,Retiger-Peppas equation fitting, analysis of in vitro release pattern of each index component.using similarity factor of f2, pairwise comparison of the four active ingredient’s vitro release profile,explore the active ingredients can not achieve a balanced release of Yukuimembranae.(3) We choose saline as the ccepted solution,bullfrog skin of abdominal wall asthe model of mucosal permeability, mucosal permeability tests conducted using Franzdiffusion cell, measured picroside Ⅰ and Ⅱ, paeonol indirubin by HPLC, measuredborneol by GC, determination of the amount of drug cumulative penetration of the receivedpool within5h,the cumulative permeation data were used to zero-order equation, an equation,Higuchi equation, Retiger-Peppas equation fitting, analysis the mucosal permeability modeof each component.Results:.(1) Cumulative release rate of picroside Ⅰ, Ⅱis96%, in vitro release profilecloser to a kinetic equation: Ln（100-Q）=-1.42t+4.07，R2=0.8700,the speed of release is649.56μg·h-1. Cumulative release rate of paeonol is81%, in vitro release paeonol closer toR-P equation: LnQ=0.82Lnt+4.89， R2=0.7612,the speed of release is37.95μ g· h-1.Cumulative release rate of indirubin is92%, in vitro release paeonol closer to a kineticequation: Ln（100-Q）=-1.02t+4.11，R2=0.8299,the speed of release is4.5591μg·h-1.Cumulative release rate of borneol is92%, in vitro release borneol closer to a kineticequation:，Ln（100-Q）=-1.11t+3.98，R2=0.7526,the speed of release is189.89μg·h-1.Mutual release profile’s similarity factor of four active ingredients of prescription betweengreater than50%,can achieve a balanced release.(2) Cumulative penetration rate of picrosideⅠ, Ⅱis24%within2h，cumulative penetration rate of picroside Ⅰ, Ⅱis40%within5h,penetration model closer to Higuchi equation: Q=20.70t1/2-6.22，R2=0.9972, the speed ofpenetration within2h is127.11μg·h-1,the speed of penetration within5h is85.88μg·h-1.Cumulative penetration rate of paeonol is14%within2h, cumulative penetration rate ofpaeonol is55%within5h, penetration model paeonol closer to R-P equation:LnQ=1.16Lnt+1.99，R2=0.9922,the speed of penetration within2h is4.39μg·h-1.,the speedof penetration within5h is6.61μg·h-1.Cumulative penetration rate of indirubin is17%within2h, cumulative penetration rate of indirubin is36%within5h, penetration modelindirubin closer to a kinetic equation: Ln（100-Q）=-0.09t+4.59，R2=0.9947, the speed ofpenetration within2h is0.41μg·h-1,the speed of penetration within5h is0.38μg·h-1.Cumulative penetration rate of borneol is9%within2h, cumulative penetration rate ofborneol is46%within5h,penetration model borneol closer to R-P equation:LnQ=1.04Lnt+1.65，R2=0.9735, the speed of penetration within2h is2.13μg·h-1,the speedof penetration within5h is4.04μg·h-1.Conclusion: In this paper, we establish the method for the determination ofpicroside,paeonol indirubin, borneol in Yukui membranae. By in vitro experiments and in vitro release mucosal permeation experiments, Analysis two more indicators of fat-solubleingredients Indirubin, borneol and two water solubility index components picroside picrosideⅠ and Ⅱ, paeonol in vitro release model and in vitro model of mucosal permeability.Achieve a balanced multi-index components released, the rate of drug release significantlygreater than rate of drug permeation by mucosa, can meet the requirements of drugconcentration to mucosal absorption,embodies the characteristics of traditional Chinesemedicine multi-component drug synergy.