Preparation And Evaluation Of Aconitine Nanoemulsion Gel Patc

Objective: In order to enrich the dosage forms of Aconitine A and improve the existing problems in the current administration of Aconitine A,we plan to prepare Aconitine A into oil-in-water nano-emulsion,increase the solubility of Aconitine A,and improve its stability and transdermal rate.On this basis,nano emulsion was dispersed into water-soluble polymer matrix to make gel plaster.Kusnetin A gel plaster can improve the bioavailability of transdermal drug delivery,reduce the fluctuation of blood drug concentration,extend the drug release time,reduce the number of drug applications,and reduce the side effects,which is particularly suitable for the treatment of chronic diseases such as rheumatoid arthritis.At the same time,Kusnetin A gel plaster is mainly aimed at the diseases with local pain.After administration,the drug can reach the affected area directly,avoid the toxic and side effects caused by systemic administration,and achieve safe,efficient,stable and convenient administration.Methods: 1.To study the formulation and preparation process of aconitine A nano-emulsion,and evaluate its quality: select the appropriate oil phase,emulsifier and co-emulsifier through the equilibrium solubility test,and then prepare aconitine A nano-emulsion by water titration and microfluidization homogenization,optimize the formulation of aconitine A nano-emulsion by pseudo-ternary phase diagram combined with Box-Behnken response surface,and investigate its particle size distribution and stability.2.Optimizing the matrix formulation of kusnezocin A nano emulsion gel plaster:Based on the single factor experiment,Plackett Burman design and the steepest climb experiment,the matrix formulation of kusnezocin A nano emulsion gel plaster was optimized using Box Behnken response surface method,with the amount of glycerol,tartaric acid and purified water as variables,and the comprehensive scores of initial viscosity,viscosity retention and sensory evaluation as evaluation indicators.3.In vitro release and in vitro transdermal study of kusnetin A nano emulsion,kusnetin A gel patch and kusnetin A nano emulsion gel patch: establish the content determination method of kusnetin A nano emulsion gel patch,conduct in vitro release test through dialysis bag and Franz diffusion cell,compare the in vitro release of three different kusnetin A dosage forms,and conduct in vitro transdermal test through artificial skin and Franz diffusion cell,Compare the transdermal permeability of three different dosage forms of Aconitine A.Results: 1.Determine the optimal formula of Aconitum nitidum A nanoemulsion:the mass ratio of emulsifier and co-emulsifier is 1 ∶ 1,the proportion of oil phase is8%,the proportion of emulsifier is 11%,the homogenization pressure is 28000 psi,the prediction result of average particle size is 60.25 nm,the result of laser particle size analyzer is(60.55 ± 0.88 nm),the polydispersity index is(0.233 ± 0.22),and the Zeta potential is(-28.5 ± 0.34 mv);The nano-emulsion is relatively stable at low temperature.2.To determine the optimal prescription of kusnezocin A nano emulsion gel plaster: glycerin 40.877 g,tartaric acid 0.294 g,purified water 42.491 g,with a comprehensive score of 94.937 points,to prepare a gel plaster with good uniformity,high viscosity,good skin tracking and excellent coating.3.Release rate of Aconitine A nanoemulsion(cumulative release 437.4692 ±6.9281 μ G · cm - 2,release rate 91.53%)is the fastest,kusnezocin A nano emulsion gel paste(cumulative release amount 342.8239 ± 5.2358 μ G · cm - 2,the release rate is 71.36%),followed by kusnezocin A gel paste(the cumulative release amount is281.6525 ± 2.804 μ G · cm - 2,release rate 58.64%)is the slowest,and the release process of kusnetin A in kusnetin A nano emulsion conforms to Higuchi equation,while the release process of kusnetin A in kusnetin A gel paste and kusnetin A nano emulsion gel paste conforms to the first order equation;The cumulative permeation amount of aconitine A nanoemulsion is(192.2777 ± 3.2344)μ G · cm - 2,the skin penetration rate is 56.70%,which is 2.23 times and 1.58 times of kusnetin A gel paste and kusnetin A nano emulsion gel paste,respectively.The release process of kusnetin A in kusnetin A nano emulsion conforms to the first order equation,and the release process of kusnetin A in kusnetin A gel paste and kusnetin A nano emulsion gel paste conforms to the Higuchi equation and the first order equation.Conclusion: Kusnezocin A nano emulsion can significantly improve the transdermal permeability and stability of kusnezocin A,and the preparation of kusnezocin A nano emulsion into gel plaster can improve its transdermal permeability,achieve the purpose of slow release,and can be used for the treatment of rheumatoid arthritis.