Studies On α-asarone Immediate-Release Tablets

As a poorly soluble drug, a-asarone’s oral dosage forms (tablets or capsules) showed low dissolution and low bioavailability. In this study, a sealed-heating method was used to prepare α-asarone-β-CD inclusion complex to improve the solubility of the drug. Influences of inclusion temperature, time and balance humidity on inclusion rate were investigated. The conditions for inclusion were optimized by orthogonal experiments. The formation of inclusion was verified by X-ray diffraction (XRD), Fourier transform infrared spectroscopy (FT-IR) and differential scanning calorimetry (DSC). Immediate-release tablets of a-asarone inclusion were furher prepared in this study. The influences of some excipients on dissolution of a-asarone-p-CD complex immediate-release tablets were investigated.The preparation of immediate-release tablets were optimized. The stability of a-asarone inclusion immediate-release tablets was investigated by the accelerated test in this paper. Optimal condition for inclusion was obtained by orthogonal design:80℃,2h, balance humidity30%.The optimized tablets composition was:α-asarone-β-CD complex (72.8%, w/w), silica powder (0.2%, w/w), CMS-Na (5%, w/w), magnesium stearate (0.5%, w/w), MCC (20.5%, w/w), PEG6000(1%, w/w). The in vitro dissolution of this inclusion immediate-release tablets was significantly improved, which was over90%at40min; while that of the physical mixture was only45%.Stability testing results showed that a-asarone inclusion immediate-release tablets were unstable at40℃, relative humidity75%. There were drug crystals precipited on the surface of the tablets.Drug dissolution was reduced with the extension of time.Prior to a-asaron’s intestine absorption experiment, the adsorption of drug onto the delivery pipeline-silicone rubber tube was inspected. The results showed that a-asarone had serious adsorption in the silicone rubber tube. The adsorption of some other insoluble drugs (paeonol, indomethacin, puerarin, osthol) in silicone rubber tube was also investigated in various pH buffers. In the range of pH3.5-7.0, osthol showed the most serious adsorption. In pH7.5buffer solution, a-asarone showed the most serious adsorption of80%(120min). In this study, HPLC analytical method for a-asarone in rat plasma was also established.