Research And Development Of The Osthole Microemulsion And Microemulsion Gel And The In Vitro Absorption Mechanism

Objective:Microemulsions are composed of an oil phase,a surfactant,and a co-surfactant mixed with distilled water at a certain ratio,and can form a thermodynamically stable system spontaneously.It can not only improve the solubility of the drug,but also avoid the adverse reactions of the drug.This experiment is to study the production of osmanthrin microemulsion,to determine the characteristics of microemulsion and to measure and calculate the transdermal concentration and permeability accumulation of Osthole microemulsion and microemulsion gel.Evaluate the effect of in vitro transdermal microemulsion and microemulsion gel in transdermal application,and compare it with the formulations already on the market to provide a basis for the research of basic clinical medicine.Methods:In the production of microemulsions,the selected oil phase,surfactant,and co-surfactant are screened for solubility,and then the transmittance of the oil phase to each surfactant and co-surfactant is detected.After selecting the appropriate phases,use the water droplet method to titrate different proportions of the oil phase and different proportions of the surfactant and co-surfactant(S_mix)to determine the oil phase,S_mix,and the ratio of the water phase to draw a pseudo-three Yuan phase diagram.After measuring the area of the pseudo-ternary phase diagram and the stability of the microemulsion,the particle size,zeta potential,pH,conductivity,and infrared spectrum of the four microemulsions were screened out,and four different ratios were measured.The microemulsion was tested in vitro for 24 hours,and the microemulsion with the largest transdermal volume was selected as the best microemulsion formula.Carbom 940 was used to prepare gel formulations.The optimal microemulsion gel formulation was screened by transdermal in vitro.The state of microemulsion and microemulsion gel was detected by differential scanning calorimeter and transmission electron microscope.The optimal microemulsion gel was compared with the commercially available Osthole cream in vitro for transdermal experiments to compare the subcutaneous drug concentration.Results:Therefore,the oil phase?IPM,ethyl oleate?,surfactants?Kolliphor HS-15,Tween 20,Tween 80,Kolliphor RH40,Cremophor EL-35?were screened based on the solubility data.Surfactant?Transcutol-P,Labrasol?,the light transmittance of Tween 20 and the oil phase is 67%,which indicates that the Tween20 and the oil phase are not well combined,and the other combined light transmittances are greater than 90%.The ternary phase diagram screened out four microemulsions with different proportions of each phase.The particle size of the blank microemulsion is 12 nm-29.2 nm,the particle size of the drug-containing microemulsion is 86.9nm,the zeta potential is between-38.32 mv to-38.51 mv,and the pH is in a neutral state.For a 24-hour transdermal experiment Analysis showed that the drug concentration in the ME-1 solution was 636?g/mL.The receiving solution concentration of ME-2 was 251.5?g/mL,the receiving solution concentration of ME-3 was 524?g/mL,and the drug concentration of ME-4 in the receiving solution was 595.5?g/mL.The permeability(J_ss),permeability coefficient?K_p?,and permeability accumulation(Q₂₄)of the four formulations were calculated.The permeability accumulation of ME-1 is 4.27 mg/cm²,ME-2 is 1.79±0.22 mg/cm²,ME-3 is 3.815±0.045 mg/cm²,and ME-4 is 3.89±0.01 mg/cm².Transdermal experiments were performed again in microemulsions with carbohydrate ratios of 1%,1.5%,and 2%,respectively.The permeability accumulation of 1%microemulsion gel is 2.08±0.140 mg/cm²,the permeability accumulation of 1.5%microemulsion gel is 0.28±0.005 mg/cm²,and the permeability accumulation of 2%microemulsion gel is 0.11±0.007 mg/cm².The differential scanning calorimeter was used to analyze the water state of the microemulsion gel,which all met the requirements for the stability of the water structure.Transmission electron microscopy showed that the size and particle size of the microemulsion under the electron microscope were consistent with the conditions,and the size was uniform,and the particle size was 51.84 nm.The particle size is less than 100 nm.Conclusions:The oil phase to be selected is selected according to the size of the solubility and the light transmittance.The microemulsion selected from the pseudo-ternary phase diagram phase diagram produced by the surfactant and co-surfactant has good stability,and the microemulsion is translucent and uniform.And there is a blue light liquid.The solubility of IPM is the highest in the oil phase.The solubility of Kolliphor HS 15 Tween 80 in the surfactant and Transcutol-P Labrasol in the co-surfactant is the largest.For all oil phases,surfactants and co-surfactants,The four ratios determined by titration with water were 1:1,2:1,3:1,and 3:2 for Smix,and the ratio of Osthole to microemulsion was 2%.It can be completely dissolved in the microemulsion,and the measured data such as particle size and zeta potential meet the requirements,and the pH value is also suitable for external skin use.ME-1 has the highest transdermal concentration and the highest permeability accumulation in transdermal microemulsion absorption.ME-1 was added to different concentrations of carbomer for transdermal experiments in vitro.Experiments show that the microemulsion gel with 1%carbomer has the highest transdermal concentration and the highest permeability accumulation.Compared with the market Osthole ointment,it was found to be significantly higher than its Osthole content.And the microemulsion gel had the highest subcutaneous drug content.It provides the scientific research basis for the later clinical application practice.