betadex and ligustilide

To improve the stability and oral bioavailability of Z-ligustilide (LIG), the inclusion complex of LIG with hydroxypropyl- β-cyclodextrin (HP-β-CD) was prepared by the kneading method and characterized by UV-Vis spectroscopy, differential thermal analysis (DTA) and Fourier transform infrared (FTIR) spectroscopy. LIG is capable of forming an inclusion complex with HP-b-CD and the stoichiometry of the complex was 1:1. Stability of the inclusion complex against temperature and light was greatly enhanced compared to that of free LIG. Further, oral bioavailability of LIG and the inclusion complex in rats were studied and the plasma drug concentration-time curves fitted well with the non-compartment model to estimate the absolute bioavailability, which was 7.5 and 35.9 %, respectively. In conclusion, these results show that LIG/HP-β-CD complexation can be of great use for increasing the stability and biological efficacy of LIG.

Topics: 2-Hydroxypropyl-beta-cyclodextrin; 4-Butyrolactone; Animals; beta-Cyclodextrins; Biological Availability; Drug Stability; Male; Rats; Rats, Sprague-Dawley; Spectroscopy, Fourier Transform Infrared; Temperature

In order to investigate the rationality of formulation, the absorption behavior of volatile oil from rhizome of ligusticum chuanxiong (VOC) was compared with that of beta-cyclodextrin inclusion complex and self-microemulsifying soft capsule (SMESC). To study the properties of intestinal absorption in situ of SMESC, a series of studies were carried out including the absorption at different concentrations, at different intestinal regions and under different bile secretion conditions. The samples of the perfusion solution were collected at certain intervals. Ligustilide (LD) was chosen as marker component of VOC and the concentrations of which in the perfusion samples were determined by HPLC method. The results demonstrated that the absorption of LD in SMESC was the best and the absorption of VOC increased apparently (P < 0.001). The absorption of LD at concentration of 400 microg x mL(-1) was better than that at 200 microg x mL(-1) and 100 microg x mL(-1) (P < 0.001), while there was no significant difference between the absorption at concentrations of 200 microg x mL(-1) and 100 microg x mL(-1). The absorption of SMESC was not apparently influenced by bile secretion. SMESC could be absorbed in whole intestinal segments. The absorption rate constants (Ka) or apparent permeability coefficients (Papp) of SMESC showed duodenum > jejunum > colon = ileum. Ka and Papp of SMESC at duodenum were significantly higher than that at the other regions of intestine (P < 0.001).

Topics: 4-Butyrolactone; Animals; beta-Cyclodextrins; Capsules; Duodenum; Emulsions; Female; Intestinal Absorption; Ligusticum; Oils, Volatile; Plants, Medicinal; Rats; Rats, Wistar; Rhizome