Preparation Of Glabridin-Nicotinamide Nanoemulsion By High-Energy Emulsification

Glabridin(Glab)is the main isoflavone component of glycyrrhiza glabridin L,a herbal plant.It has antioxidant,free radical scavenging,inhibition of tyrosinase and other biological activities,known as "whitening gold" in the cosmetics industry.However,its poor water solubility and instability under light limit application in transdermal preparations.In this study,high pressure homogenization method(HPH)and high speed shear ultrasound method(HSSU)were designed to prepare glabridin-nicotinamide nanoemulsion(G-N-NE),which improved the solubility and stability of Glab,and promoted the skin penetration of Glab.In this study,a high performance liquid chromatography(HPLC method)was first established to determine the content of Glab and NAM in G-N-NE.The solubility of Glab and NAM in different dissolution media,the stability of bulk drug and the solubility of Glab in excipients were investigated.The ability of excipients to form nanemulsions and the effect of Glab on tyrosinase activity were preliminarily explored.The results showed that the oil-water partition coefficients of Glab were4.33,respectively;both Glab and NAM are relatively stable in weakly acidic and neutral solutions,but unstable in alkaline solutions.The emulsification test results of excipients show that Tween 80 has the best emulsifying ability,and isopropyl myristate(IPM)has the best emulsifying effect;the tyrosinase inhibition test results show that Glab was a very effective tyrosinase inhibitor.G-N-NE was prepared by HPH method and HSSU method respectively.Through the investigation of pseudo-ternary phase diagram and experiments of various influencing factors,and optimized the formulation process according to Box-Behnken response surface design method,the optimal formulation process of HPH was determined as: Mass pressure 1,000 bar,6 cycles,NAM 1.00 g,phenoxyethanol and ethylhexylglycerol each 0.50 g,Glab 0.15 g,IPM 1.00 g,ODO 1.00 g,glycerol 3.25 g,Tween 80 9.75 g and water;The optimal formulation process of HSSU is: shearing speed of 14,000 r·min-1,shearing time of 5 min,ultrasonic intensity of 80%,ultrasonic time of 6 min,NAM 1.00 g,phenoxyethanol and ethylhexylglycerol All were 0.50 g,Glab 0.11 g,IPM 0.86 g,ODO 1.28,glycerol 3.21 g,Tween 80 9.64 g and water.Nanoemulsions were prepared according to the optimized formulation process,then verifying model and formulation.The Glab encapsulation efficiency of the nanoemulsion prepared by HPH reached 98.12%,the average particle size was51.61 nm,and the PDI was 0.143;the Glab encapsulation efficiency of the G-N-NE prepared by HSSU reached 95.18%,the average particle size was 42.98 nm,and the PDI was 0.118.The G-N-NE prepared by HPH and HSSU methods were characterized in terms of appearance,microscopic morphology,particle size,PDI,Zeta potential and transdermal effect.The results of transmission electron microscopy and stability tests showed that the nanoemulsions prepared by HPH and HSSU were clear.Transparent,the emulsion droplets are spherical,and the stability is good within 3 months.The transdermal test results show that the penetration effect of G-N-NE prepared by HSSU is about 1.5 times that of G-N-NE prepared by HPH,indicating that the preparation of G-N-NE using HSSU can be more effective.Effectively enhance skin penetration of Glab and NAM.