Preparation Of The Tablet Of Rhizomes Of Chuanxiong Components And Research On Its Pharmacokinetics In Rats

The tablet of rhizomes of chuanxiong components is multi-component Chinese Medicine and composed of sodium ferulate and ligustrazine hydrochloride, which are effective substances of Ligusticum chuanxiong Hort. In this study, preformulation research, optimization of preparation technology, research of quality control method, pharmacokinetics in rats and the in vitro and in vivo correlation have been performed.An high performance liquid chromatography(HPLC) method was estbalished based on both the physical and chemical properties of sodium ferulate, ligustrazine hydrochloride. Methodological study results indicated that the method was simple, accurate, reproducible, and can be used to quantitative detection of bulk drug on sodium ferulate and ligustrazine hydrochloride.Single factor test and orthogonal design test was used to screen the dosage of ethanol, sodium thiosulfate and ethylenediamine tetraacetic acid disodium, with the content of tablet hardness and disintegration time as index.The addition ratio of microcrystalline cellulose is 1:0.8(compared with quality of sodium ferulate, the same below), polyvinylpolypyrrolidone is 1:0.3,10% starches is 1:0.75 and 0.2% magnesium stearate. The tablet hardness and disintegration time of 3 batches of The tablet of rhizomes of chuanxiong components met quality requirements, which was proved convenient and feasible by validation test.To carry out the dissolution experiments by the combination method of area under the absorbance-wavelength curve (AUAWC) and HPLC. The cumulative dissolution in vitro of total composition, sodium ferulate and ligustrazine hydrochloride of tablet of rhizomes of chuanxiong components at 90 min was 99.84%,99.74% and 100.13% respectively in water.In vivo, based on the random two-way cross-over design, SD rats werebe regarded as the research object, which were given the injection of rhizomes of chuanxiong components and the same amount of drug suspension of tablet of rhizomes of chuanxiong components by gavage, respectively. Blood samples were collected at 5,10,20,30,60,90,120,180,240 min after the administration. Plasma concentration of the total components, sodium ferulate, and ligustrazine hydrochloride of the two preparations of Chuanxiong components in rats was measured by AUAWC combined with HPLC. Pharmacokinetic parameters and absolute bio availability were calculated by DAS 2.0.After ig administration, AUC0-∞ of total components was (77.218± 13.492) mg·min/L by AUAWC and AUC0-∞ of total component was (169.775±18.252) mg·min/L for iv injection. The absolute bioavailabilities of total composition was 46.17%. As for ig administration, AUC0-∞ of sodium ferulate and ligustrazine hydrochloride is (69.134±4.853) and (16.422±2.584) mg·min/L. As for iv injection, AUC0-∞ of them were (155.244±28.994) and (36.754±6.645)mg·min/L by HPLC, respectively. The absolute bioavailabilities of ig administration were 44.53% and 44.68%, respectively. The tablet of rhizomes of chuanxiong components had a good correlation between the in vitro dissolution and the in vivo absorption percentage.Through quality control method of tablets, the labeled amounts of sodium ferulate and ligustrazine hydrochloride were initially determined to be 100 mg,50 mg respectively. Content of each component should be within the range of between 95% to 105% of the labeled amount.