Preparation And Evaluation Of Sweet And Bitter Microemulsion Ge

Objective:the formula used in this experiment which composed of licorice,sophora alopecuroides and mentha is a clinical experience prescription for the treatment of chronic eczema.The formula not only has a clearing heat and detoxicating effect,but also has a remozing dampness to relieve itching effect and it’s clinical use is extract by water for external washing,mainly used for the symptoms of hot and humid itching and the curative effect is clear.To increase the solubility of the essential oil in the formula used to treat chronic eczema clinically,to improve its efficacy in treating chronic eczema and to improve the patients’ compliance with the usage,the formula was made into a microemulsion gel formulation and make relevant evaluations and provide some reference for the development of new drug delivery system of Chinese herb formula.Methods:(1)Study on the extraction technology of Ganku microemulsion-based gel prescription:with single factor test combined with orthogonal test,the extraction process parameters of licorice was optimized with the transfer rate of glycyrrhizic acid as an evaluation index;with the transfer rate of oxymatrine and oxysophocarpine as evaluation indexes,the influencing factors were filtered by the Plackett-Burman design method,the extraction process parameters of sophora alopecuroides were optimized by the BoxBehnken response surface design method.(2)Study on the moulding techniques of Ganku microemulsion-based gel:the essential oil was used as the oil phase of the microemulsion and the extract was used as the water phase,we obtained the microemulsion area and maximum ratio of water capacity by plotting pseudo-ternary phase diagram,and then determined appropriate surfactant,cosurfactant and Km value,the microemulsion prescription was optimized by Doptimal design method with particle size and skin retention of active ingredients as the index;the single factor test was used to optimize the type,dosage,adding way and the amount of moisturizer.(3)Study on in vitro release behaviours of Ganku microemulsion-based gel:the modified Franz difusion cell method was used to evaluate the in vitro release behaviours of microemulsion-based gel with glycyrrhizic acid,liquiritin and oxymatrine as evaluation indexes.(4)Study on the skin irritation and preliminary pharmacodynamics of Ganku microemulsion-based gel:investigate whether Ganku microemulsion-based gel has skin irritation by observing the reaction of guinea pig skin when apply microemulsionbased gel;the mouse model with delayed hypersensitive eczema was selected to evaluate the efficacy of different formulations for treating chronic eczema.(5)Determination of physical and chemical properties and preliminary quality standards of Ganku microemulsion-based gel:investigate the preliminary stability of Ganku microemulsion-based gel and inspect its pH and viscosity;establish the TLC identification methods of licorice and sophora alopecuroides in formulation;establish HPLC methods for determinations of glycyrrhizic acid,liquiritin and oxymatrine in formulation.Results:(1)The extraction technology of Ganku microemulsion-based gel prescription:optimum extraction technology of licorice in the prescription was extracted 2 times with 10-fold the amount of 60%(v/v)ethanol for 1 hour each time;optimum extraction technology of sophora alopecuroides was extracted 4 times under 40℃ with 12-fold the amount of 60%(v/v)ethanol for 2 hour each time;Mentha was directly instead of peppermint oil.(2)Moulding techniques of Ganku microemulsion-based gel:①The optimum composition of Ganku microemulsion:Tween-80:9.4%(w/w),absolute ethanol:9.4%(w/w),peppermint oil:1.0%(w/w),0.5 g·mL-1 extract:80.2%(w/w).②The optimum composition of Ganku microemulsion-based gel:carbomer-940:2.0%(w/w),triethanolamine:2.1%(w/w),glycerol:9.0%(w/w),Ganku microemulsion:86.3%(w/w).③The preparation of Ganku microemulsion-based gel:the preparation was divided into two parts:the preparation of microemulsion and the preparation of gel.To obtain Ganku microemulsion,tween-80,absolute ethanol and peppermint oil were mixed in terms of proportion and stirred evenly,then 0.5 g·mL-1 extract was added to the mixed system and stirred evenly;CP-940 was sprinkled to the surface of the microemulsion and set aside overnight to be fully swollen,stirring until evenly while dropping the amount of triethanolamine solution into the mixed system,Ganku microemulsion-based gel was done and it is brown translucent Gel-like preparation.(3))Study on in vitro release behaviours of Ganku microemulsion-based gel:in vitro release behaviour of liquiritin in Ganku microemulsion-based gel conformed to the Hixcon-Crowell kinetics,the equation is(1-Q)1/3=-0.345 6t+1.000 2,and the cumulative release rate of 24 h was(12.4±1.5)%;in vitro release behaviour of glycyrrhizic acid conformed to the Ritger-Peppas kinetics,the equation is lnQ=0.7910lnt-4.560 6,and the cumulative release rate of 24 h was(9.1±0.2)%;in vitro release behaviour of oxymatrine conformed to the Hixcon-Crowell kinetics,the equation is(1Q)1/3=-0.007 4t+0.982 4,and the cumulative release rate of 24 h was(47.9±1.0)%.(4)The skin irritation and preliminary pharmacodynamics of Ganku microemulsionbased gel:in skin irritation experiment,there was no edema or erythema in the integral skin group and the damaged skin group,that is,neither the Ganku microemulsion or the Ganku microemulsion-based gel has skin irritation;in pharmacodynamic experiment,the Ganku microemulsion-based gel significantly reduced the ear swelling rate of mice(P<0.05),and there was no significant difference between the Ganku microemulsion-based gel and positive drug group(P>0.05),the anti-inflammatory effect is better.(5)Physical and chemical properties and preliminary quality standards of Ganku microemulsion-based gel:Licorice and Sophora alopecuroides in the Ganku microemulsion-based gel could be detected by TLC and the negative samples have no interference;the provision of liquiritin in the preparation shouldn’t be less than 615μg·g-1 according to the results of HPLC,the provisions of glycyrrhizic acid and oxymatrine shouldn’t be less than 3 000 μg·g-1 and 715 μg·g-1 respectly;the related examination of the Ganku microemulsion-based gel was carried out to conclusion that the pH value of the preparation should be between 5.15～6.30 and viscosity of the preparation should be between 28 000～34 000 mPa·S.Conclusions:the Ganku microemulsion-based gel can solve the problem of low solubility of essential oil in the prescription and the moulding technique is stable and feasible.It have high security,can effectively alleviate the symptoms of chronic eczema and it can lay the foundation for the further development of the prescription.