Study On Weisu Microemulsion Sustained-release Gel Drug Delivery System

Objective: Most gastrointestinal diseases are chronic diseases,which need long-term medication..The marketed Chinese medicine Weisu Granules has a significant effect in treating chronic gastritis and gastric ulcer.In order to prepare a new dosage form of traditional Chinese medicine with a sustained release effect.This study used Weisu granules as a model drug and used an in-situ gel delivery system to form a gel in the stomach and adhere to the gastric mucosa to increase its drug retention time and achieve a slow-release effect.Through microemulsion technology,the instability of volatile oil and water extract in one system can be solved.This study provide new ideas for the modernization of traditional Chinese medicine preparations.Method: 1.The extraction process includes two parts: volatile oil extraction process and water extraction process.The extraction process of volatile oil adopts orthogonal test method to optimize the soaking time of medicinal materials,extraction time,amount of water content of crude drugs.The extraction rate of volatile oil was used as the evaluation index water content of crude drugs.The medicinal residue and other medicinal materials were mixed in water for decoction.The contents of hesperidin,naringin,neohesperidin and dry paste rate were used as evaluation indexes to screen the water extraction process.2.The molding process includes the selection of gel matrix and the selection and optimization of microemulsion prescriptions.The gel concentration of ion-sensitive in-situ gel matrix of deacetylated gellan gum under suitable conditions was screened by single factor test.The deacetylated gellan gum solution was used as the water phase,and the pseudo-ternary phase diagram was drawn by the water drop method.To screen the proportion and types of auxiliary materials such as oil,surfactant and co-surfactant.Central composite design-response surface methodology was adopted to optimize the prescription of Weisu microemulsion in situ gel.3.The quality evaluation indicators include the physical and chemical properties,identification and drug loading of the prepared microemulsion sustained-release in-situ gel.Physical and chemical properties were investigated including particle size distribution,Zeta potential,p H value and viscosity of the prepared microemulsion.The initial stability of the microemulsion in situ gel was investigated.TLC was used to identify perilla stem,cymbidium,tangerine peel,citron,citroen,fructus aurantii and areca catech.The contents of naringin,hesperidin and neohesperidin were determined by HPLC.Determine the loading capacity of the microemulsion gel.4.In vitro and in vivo release behavior of sustained release in situ gel delivery system of weishu microemulsion was investigated.The paddle method was used for the in vitro release test.The filmless dissolution method was used to investigate the corrosion and release behavior of the preparation.Through animal experiments,the release behavior of Weisu microemulsion sustained-release in situ gel in rats was determined.The content of naringin,and neohesperidin was used as the evaluation index to determine the release behavior of the preparation.Result: 1.Perilla stem,cymbidium,tangerine peel,citron,citroen,fructus aurantii plus10 times the amount of water,steam distillation method to extract volatile oil for 7 hours.Then,the volatile oil is collected.Decoction of medicinal residue with areca catech and endothelium corneum gigeriage galli in water for two times.The first time with 10 times water for 2 hours.The second time with 6 times water for 1 hour.The decoction concentrated to a relative density of 1.26～1.29(70～80 ℃).2.The concentration of the deacetylated gellan gum solution with single factor screening is 0.3%.The surfactants and co-surfactants screened by the pseudo-ternary phase diagram are polyoxyethylene hydrogenated castor oil and polyethylene glycol-400,respectively.Central composite design-response surface methodology was carried out to optimize the formulation process with the solution particle size and PDI as the indexes.The final results indicate that the best prescription ratio is volatile oil: polyoxyethylene hydrogenated castor oil: polyethylene glycol-400 = 1:3:1,added 0.2% stevia,0.2% ethyl p-hydroxybenzoate.The concentrate and 0.3% deacetylated gel solution were added to the above mixture and mixed to produce 333 g microemulsion in-situ gel.3.The results of in vitro dissolution test and non-membrane dissolution test showed that the cumulative dissolution rate of the drug had a strong linear relationship with the release rate.The metabolism of naringin,hesperidin and neohesperidin best conforms to the first-order kinetic equation.The release methods of the three active ingredients are mainly corrosion,supplemented by diffusion,which shows that Weisu microemulsion in situ gel can prolong the drug release time well under artificial gastric juice conditions to achieve long-term efficacy.The metabolism of the drug in rats also has a significant slow-release effect.Weisu microemulsion in situ gel preparation is not irritating to rat gastric mucosa.Conclusion: The test results show that the preparation process of Weisu microemulsion in situ gel is reasonable and feasible.The preparation has certain sustained release characteristics.