| AbstractQH917 is a new artminsin derivative and active against Schistosoma japonicum. Due to the poor water solubility, its bioavailability was unsatisfactory. The development and application of QH917 SMEDDS in this study promoted the dissolution rate and enhanced the bioavailability significantly. Moreover, in order to solve the high bioavailability variability and food effect existing in this delivery system, in vitro dissolution, in situ permeability and in vivo absorption tests of QH917 SMEDDS were carried out respectively. The results accepted proved to be valuable for the investigation and development of such dosage forms.The pre-formution study showed that MCT had the solubility of 79．80mg(?)ml for QH917, which was higher than other choosed oils. The logarithm of apparent partition coefficients of QH917 in octanol/0．1 mol(?)L HCl,octanol/water and octanol/pH 6．8 PBS were 0．66,1．70 and 1．66, respectively, indicating that QH917 was lipophilic.In the formulation study, MCT, which had the biggest solubility of QH917, was used as oil. Cremophor RH40 and ethanol were selected as surfactant and cosurfactant respectively after the compatibility study of MCT and surfactants, comparison of emulsification capability of different surfactants, and drawing of the pseudo-ternary phase diagrams.The effects of oil, surfactant, cosurfactant, Km, and drug on QH917 SMEDDS were then investigated. Central composite design-response surface methodology was utilized to optimize the ratio of these vehicles. The effects of ionic strength, food, pH, rotation speed and medium volume on drug release of the optimized formulation were evaluated under conditions simulating in vivo physiological situations. According to Analysis of Variance, The release of QH917 from the optimized formulation was nearly unaffected by these factors.In situ intestinal perfusion studies were consequently undertaken to assess the membrane permeability of QH917 SMEDDS. The influence of bile flow, particle size and polydispersity index were studied. The results showed that QH917 SMEDDS had good membrane permeability; bile flow had no influence on absorption of QH917．The smaller the particle size, the faster the absorption rate of the drug.The mean particle size of the optimized formulation of QH917 SMEDDS was 70．0nm, and its zeta potential was-l.69mv. The morphology of QH917 microemulsion droplets presented sphericity and uniformity under transmission electron. The stability of QH917 SMEDDS was good at room temperature with no obvious change of appearance, drug content, self-microemulsifying rate, particle size and polydispersity index.The pharmacokinetics test of QH917 in rats was performed by LC/MS/MS method. Data showed that QH917 SMEDDS could increase bioavailability of QH917 significantly compared with CMC-Na suspension and the absolute bioavailability was 42．9%. The C, T, and AUC in preprandial states, postprandial and intake lipidic diet of QH917 SMEDDS were 79．8(?)36．6, 28．6(?)16．1, 68．7(?)42．9(ng/ml); l.83(?)0．75, 3．00(?)0．89, 3．83(?)1．17(h); 210．5(?)52．7, 132．2(?)55．8, 408．7(?)225．6(ng(?)h/ml) for the reference formulation, and 90．5(?)22．1, 48．4(?)21．4, 70．3(?)10．9(ng/ml); 1．93(?)0．66, 3．00(?)0．63, 3．67(?)0．52(h); 276．2(?)45．6, 252．7(?)37．2, 412．5(?)63．1(ng(?)h/ml) for the optimized formulation. There was no statistic significance of AUC for the postprandial and intake lipidic diet groups compared with the preprandial state for the optimized formulation(p > 0．05) . When comparing with the reference formulation, the optimized formulation of QH917 SMEDDS in all diet conditions exhibited less pharmacokinetic variability and diminished food effect.
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