Preparation Of Nobiletin Ion-sensitive In Microemulsion-based Gel

Objective: To prepare nobiletin ion-sensitive in microemulsion gel.Methods:(1)Using UV scanning method for the determination of nobiletion wavelength.(2)HPLC is determined by drawing standard curve,specificity and stability of nobiletion.(3)The microemulsion formulation was screened and optimized by solubility test and pseudo-ternary phase diagrams.The quantity of gel matrix was selected through viscosity measurement.(4)Orthogonal design was employed to transdermal diffusion test in rabbits? nasal mucosa in vitro,the cumulative permeation quantity and permeation rate of nabiletin were considered as indexes to optimize the optimal prescription.(5)The micro-morphology,Zeta potential,particle size,pH and drug content were evaluated.(6)Behavior of the drug release was studied by modifying diffusion cell and mechanism of the drug release was studied by membrane-less model.(7)To investigate microemulsion gel preliminary stability by observin-g reserved sample.(8)By using SD rats nasal mucosa slices after HE staining to study the irritation of the nasal mucosa of the microemulsion gel;The ciliotoxicity of nabiletin microemulsion gel was taken on toad palate mucosa cilia.Results:(1)The UV detection wavelength of nabiletin was 332 nm.(2)Nobiletin in solvent had a good liner relationship between peak area and concentration in which range was 6.0~120 ?g/mL;nobiletin in release medium had a good liner relationship between peak area and concentration in which range was 3.0~96 ?g/mL;with good instrument specificity and precision;at room temperature,nobiletin was relatively stable in 24 hours.(3)The best formulation of microemulsion gel was 0.9% nobiletin,0.8% MCT,31.5% cremophorEL-35,10.5% PEG-400 and 50% purified water;0.3% deacet-ylated gellan gum solution 50%.(4)The results showed that the influence order of different penetration enhancers on cumulative permeation quantity and permeation rate of nabiletin were as follow: azone > borneol > propanediol,while azone had significant difference(P<0.05),It was evidently that the prescription of 2% azone,2% borneol and 1% propanediol could be used as the compound penetration enhancer.(5)Observed under the transmission electron microscope,the micro-morphology particle of microemulsion and microemulsion-based gel were spherical and disperse evenly,size of microemulsion and micr-oemulsion-based gel were below 50 nm,Zeta potential of-5.58±0.2 mV and-5.68±0.2 mV,pH value of 6.64±0.20,drug content of 8.665 mg/mL.(6)Membrane-less model showed erosion rate of microemulsion gel was low and not linearly correlated with the drug release rate(r=0.9387);diffusion cells results showed the cumulative release rate of microemulsion gel in 12 hours was 86% which followed the Higuchi equation.(7)The results of stability showed that the microemulsion gel should be stored at refrigerated place,appearance,viscosity,pH and drug content did not change in 0~45 day,has a good stability.(8)Mucocal irritation and cilia toxicity showed that nobiletin microemulsion gel were non-toxic to nasal cilia,and almost non-irritation to mucocal.Conclusion: The preparation technology of nobiletin microe-mulsion gel is reasonable,reliable,quality inspection method is feasible;nobiletin microemulsion gel were non-toxic to nasal cilia and almost non-irritation to mucocal,it had a good property of drug release in vitro and showed controlled release property,and It could be used as carrier for nasal delivery system.