Puerarin Oral Micro-emulsifying Drug Delivery System

The oral delivery of hydrophobic drugs presents a major challenge because of their low aqueous solubility, which may lead to poor bioavailability. A lot of measures were used to improve the oral absorption of drugs. Modification of the physicochemical properties, such as reducing particle size of the compound , using solubilizer , solid disperser formation or incorporating the compounds into lipid vessels may be one approach to improve the dissolution rate of the drug. Surfactants play a key role in many of the novel drug delivery systems developed, such as self-emulsifying drug delivery systems(SEDDS).SEDDS are mixtures of oils, cosurfactants and surfactants, ideally isotropic, which emulsify under conditions of gentle agitation, similar to those which would encountered in the gastro-intestinal tract. When such a formation is released into the lumen of the gut it disperses to form a fine emulsion, and the mean droplet size is 100~500nm. When the concentration of surfactants is higher, it formulates SMEDDS. SMEDDS typically produce transparent and isotropic microemulsions in the lumen of the gut with a droplet size of less than 100nm.Puerarin as model drug was used to evaluate the self-microemulsification existence area and self-microemulsification efficiency. Solubility of Puerarin in various vehicles were determined. The self-microemulsification efficiency was assessed, such as self-microemlsification time, appearance, stability and particle size.The mixtures consisting of IPM as oil, with the nonironic surfactant CremphorEL and cosurfactant Ethanol were found to be optimal formulations. Some factors affecting self-microemulsification efficiency were investgated. for example, temperature ,dilution, medium. Drug capability and oil capability on the particle size in water were investigated. HPLC method was chosen to determine the content of Puerain in the prepatation. The average recovery was 100.20%, RSD was 0.28%(n=3). The influence factors of temperature and illumination was studied , and temperature accelerated test indicated the Puerain SMEDDS were stable at 40°C for 3 months. The HPLC method was adopted for determination of Puerain in plasma. In rats,the standard curve is linear in the range of 0.051-20.3 u g/ml(r=0.9999),the limit is 0.025 u g/ml. The average rate is 91.1%, the within day and between day precision ofdetermination of Puerain in plasma was 1.8% and 2.4% separately.Compared with conventional tablet, the Cmax from SMEDDS is greater .AUC were calculated using trapezoidal rule. Cmax and tmax were obtained from the raw data. TheAUC, Cmax and tmax of SEDDS and conventional tablet in this study was AUC: 466.50 Og ?min/ml), 186.99 (ug ?min/ml) ; tmaX! 47.5±6.12min,47.5±6.12min; CmaX: 4.8276 + 0.64( v g/ml), 1.88 + Q21{M g/ml). The data was disposed using the program SPSS and the AUC after oral administration of SMEDDS in the present study was significantly increased compared with the reference tablet. Compared with the conventional tablet, the relative bioavailabilty of SMEDDS was 249.48%.