Studies On Chinese Herbal Medicinal Ingredients Self-microemulsifying Drug Delivery System

Curcumin （Cur） is an active constituent extracted from Curcuma longa,it have multiple pharmacological activities including anticancer,anti-inflammatory activity, anti-oxidative effect, hypolipidemic and otherpharmacological active with few side effects. But poor solubility ofcurcumin in aqueous solution and instability remain a major barrier in itsbioavailability and clinical efficacy.Baicalein （BA）, an active constituent in the root of Scutellariabaicalensis Georgi, it has been reported to have multiple pharmacologicalactivities including antibacterial, anti-viral effect, anti-inflammatoryactivity, anti-oxidative effect, anticancer, and so on. Because of its lowwater solubility and oral bioavailability, its use in clinical field is limited.Self-microemulsifying drug delivery system （SMEDDS） is a kind ofnew drug delivery system. It has been used as a vehicle for indissolvabledrug to improve solubility and oral bioavailability, it has great prospect andapplication value.Cur and BA were chosen as the representatives, curcuminself-microemulsifying drug delivery system and baicalein self-microemulsifying drug delivery system were prepared, to improve itsoral bioavailability.PartⅠ Studies on curcumin self-microemulsifying drug de1iverysystemUV method of Cur was developed for assay. The regression equationwas A=0.1721C＋0.0075, r=0.9999, which was linear over the range of0.5⁶.0μg·mL^-1. Its precision, recovery all met the requirement oftechnology.The basic components of the formulation were determined byinvestigating the balance solubility of Cur in different excipients anddrawing pseudo-ternary phase diagrams.The prescription of Cur-SMEDDS was optimized by Single-factor test,composed of EO-Cremophor RH40-Transcutol P（30%∶52.5%∶17.5%）.Dialysis method was used to evaluate the dissolution of Cur fromSMEDDS. Result of the stability experiment indicated that Cur-SMEDDScould be kept stable at room temperature for3months.PartⅡ Studies on baicalein self-microemulsifying drug de1iverysystemUV method of BA was developed for assay. The regression equationwas A=0.0523C-0.0309, r=0.9997, which was linear over the range of4.0¹6.0μg·mL^-1. Its precision, recovery all met the requirement oftechnology. Suitable compositions of SMEDDS formulation was screened viasolubility experiment and pseudo-ternary phase diagrams. With the amountof oil phase and Km as independent variables, the formulation ofBA-SMEDDS was optimized by a central composite design （CCD）, theresponse variables were solubility and average particle size. The optimalformulation of BA-SMEDDS was comprised of ODO-CremophorRH40-Transcutol P （25%∶53.57%∶21.43%）. With BA as the referenceagent， In vitro release was investigated by a dialysis method. Result of thestability experiment indicated that BA-SMEDDS could be kept stable atroom temperature for3months.HPLC method for simultaneous determination of BA and baicalin （BG）were developed for assay. The regression equation of BA wasA=0.383C-0.0096, r=0.9992, and the regression equation of BG wasA=0.1768C＋0.0088, r=0.9999, which were linear over the range of0.05¹5.00μg·mL^-1. Its specific, precision and recovery all met therequirement of technology.To BA suspension as the reference agent, the pharmacokinetics studyof BA-SMEDDS was performed in rats and data was analysized. After oraladministration of BA–SMEDDS and BA suspension, BA were quicklymetabolized in vivo, the parent form of BA in plasma was detected in avery low level, while the metabolite BG was detected mainly in rat plasma.So the oral bioavailability of BA-SMEDDS was studied compared with BA suspension by determining BG concentration in rat plasma. The plasmaconcentration-time curves of BG showed two peaks after oraladministration of BA-SMEDDS and BA suspension. Compared with BAsuspension, t_maxof BA-SMEDDS in rat was shorted, C_maxwas increased1.63times, and AUC_0-48hwas increased1.82times. It was showed thatSMEDDS could improve the oral bioavailability of BA significantly.This study proved that SMEDDS increase the solubility and oralbioavailability of Cur and BA significantly, which met the requirement forclinical. It is a drug system with great investigating value and potentials.