Preparation And Physiological Disposition Of Xiang-Fu-Si-Wu Decoction Essential Oil Inclusion Complex

Xiang-Fu-Si-Wu Decoction (XFSWD), a famous Chinese herbal formula, is considered as an effective prescription for treating qi stagnation and blood stasis syndrome with primary dysmenorrhea. Our previous researches indicated the close correlativity between volatile components and bioactivity of the prescription. Based on the previous studies of XFSWD, inclusion complex was attempted to be used for the process of pharmaceutical preparation of XFSWD essential oil (XFSWO). This study is to investigate the effect of β-cyclodextrin (β-CD) inclusion complex on the absorption and pharmacokinetics of major components of XFSWO. The analytical results provided scientific basis for new oral preparations of XFSWD.Although the essential oil of traditional Chinese medicine (TCM) has strong pharmacological activity, but its special physical and chemical properties restrict the clinical application and curative effect. The essential oil may stimulate gastrointestinal tract and its pungent smell may result in poor oral compliance. The volatility and instability may cause difficulties to storage and quality control. The poor water-solubility may substantially decrease the absorption and oral bioavailability. On the basis of biopharmaceutics classification system, volatile components belong to class 2 with low solubility and high permeability. Dissolution is the speed limit of absorption. Cyclodextrins (CD) have hollow cylindrical structure with relatively hydrophilic surface and hydrophobic central cavity, which have been used as attractive material for drug inclusion. CD inclusion complex can be applied to improve the chemical stability, cover up bad smell, reduce the stimulation of gastrointestinal tract, make liquid drugs solidified, and improve the water solubility thus promote the drug absorption and improve its bioavailability.The cyclodextrin inclusion technology was used for XFSWO preparation research in this paper. Two kinds of material and three preparation methods were compared to obtain the best effect of inclusion. According to the experimental results, β-CD and the grinding method were selected. With orthogonal experiment, the influences of each factor on inclusion rate, yield and oil ratio were reported. The result demonstrated that the optimal technological parameters were as follows:water:β-CD 3:1 (mL:g), XFSWO:β-CD 1:6 (mL:g), inclusion time 2 h, which showed good reproducibility. The XFSWO/β-CD inclusion complex was characterized by different analytical techniques including differential scanning calorimetry (DSC), fourier transform infrared spectroscopy (FT-IR), X-ray diffraction (XRD), scanning electron microscope (SEM), and the formation was verified. The GC/MS method was established to study the chemical components and stability of XFSWO/β-CD inclusion complex. The result showed that the chemical composition of inclusion complex not obvious changed but with different content, and XFSWO/β-CD inclusion complex was more stable.The present study investigated the absorption of XFSWO/β-CD inclusion complex using Caco-2 cell monolayer model. The result revealed that the formation of inclusion complex has significantly increased the transportation and absorption of the major active ingredients than free oil. The pharmacokinetic study on rats also demonstrated that XFSWO/β-CD inclusion complex could greatly improve the oral bioavailability of XFSWO.The XFSWO/β-CD inclusion complex was successfully prepared in this study. The GC/MS method to study the stability of XFSWO/β-CD inclusion complex was first established. A sensitive and rapid UPLC-MS/MS method was developed for simultaneous quantification of senkyunolide A,3-n-butylphthalide, Z-ligustilide, dehydrocostus lactone and a-cyperone in rat plasma after oral administration of XFSWO and its β-CD inclusion complex. To the best of our knowledge, this is the first pharmacokinetic study on XFSWO and its inclusion complex by this method. In vitro and in vivo results indicated that the inclusion complex formation can significantly enhance stability, increased the transportation and absorption of XFSWO, and the delivery system can greatly improve its bioavailability, which provided foundation and basis for pharmaceutical study of XFSWD.