Preparation Of Compound Kushen Self-emulsifying Drug Delivery System

Compound Kushen Injection(CKI,also known as yanshu injection)is a traditional Chinese medicine formula which is approved by State Administration of Chinese Medicine.CKI is extracted from the roots of two medicinal herbs,Kushen(Radix Sophorae Flavescentis)and Baituling(Rhizoma smilacis Glabrae).It have many pharmacological properties,such as anti-tumor,anti-inflammation,analgesia,and immunity-enhancing activity,and so on.In the clinical application,it is used as adjuvant treatment of various cancers by improving anti-cancer efficacy and reducing the side effects of chemotherapy.However,CKI is only applied in the patients’ hospitalization by injection administration and it is unfavorable for patients’ follow-up treatment,so it is considered to prepare solid self-emulsifying drug delivery system(S-SEDDS)to improve the problem.Self-emulsifying drug delivery system(SEDDS)is an isotropic mixture of oil,surfactant and cosurfactant which is capable of forming fine O/W emulsion under gentle agitation.It can spontaneously form the small droplet size providing a large interfacial surface area and improve the dissolution and absorption.At the same time,it can increase intestinal lymphatic absorption and make drugs to avoid liver first effect.Solid self-emulsifying drug delivery system(S-SEDDS)is made by mixing the solid materials on the basis of SEDDS.S-SEDDS combine the advantages of liquid SEDDS with those of solid dosage forms,such as intestinal irritation reduction,storage stability and so on.This research was designed to prepare compound Kushen S-SEDDS,thus improving the dissolution and absorption of poor-soluble drug by utilizing a novel drug delivery system.Furthermore,it provided a possible for various forms of poor-soluble drug.This research aimed to set up a method to determine the matrine concentration of compound Kushen-SEDDS by high performance liquid chromatography(HPLC)and thin layer chromatography(TLC)was established to identify the components of baituling.It was established on the study of prescription selection and preparation technology about compound Kushen SEDDS.The components of the prescription were ensured as oleic/ethyl oleate(1:1),Tween-80 and isopropanol by testing solubility of different accessories and depicting pseudoternary phase diagram.Then the appropriate ratio of oils and mixed emulsifiers was 3:7 by different proportion compatibility study.Finally the best prescription of SEDDS were compound Kushen-oleic acid-ethyl oleate-Tween80-isopropanol(4:3:3:7:7).The best preparation technology were ensured by single factor experiment: the water-bath temperature was 37 ℃,the stirring rate was 800 r/min,the stirring time was 20 min,the ultrasonic power was 300 w,the ultrasonic time was 10 min.The average size of the prepared compound Kushen SEDDS was measured by dynamic light scattering(DLS)instrument,and the measured diameter was 76.49 nm.The results of the preliminary stability experiment showed that the compound Kushen SEDDS could be stored at the ambinent temperature.It was established about the study of solid adsorbent of compound Kushen S-SEDDS.Finally the suitable solid adsorbent was micropowder silica gel and we got the best prepration technology.The compound Kushen S-SEDDS were prepared by solid adsorption carrier method,and its quality was assessed.It was yellow particles under the srorage conditions.The average diameter was 124.2 nm and the Zeta potential was-25.4 mV.The results showed it had good stability.The results showed that the compound Kushen S-SEDDS could improve the dissolution with high stability,which may be promising in the long run.