The Preliminary Study On Sedative Sustained-Released Tablets

Ziziphi spinosae semen is the preferred hypnotics in traditional Chinese medicine. Saponin is the one of hypnosis active ingredient in ziziphi spinosae semen. We collected 878 ancient and modern prescriptions, as well as 236 related literatures, got the same result by Chinese medicine theory combined and modern statistic. Because of the low content about saponin in ziziphi spinosae semen, the processing of existing traditional compound preparation is not fining, clinical application widely but the effect faintly. To use the resource of ziziphi spinosae semen reasonably and improve the sedative effect of preparation preferably, the saponin of ziziphi spinosae semen, purity, and accumulative release percentage were taken as indexs to study on the preparation and evaluation about crude drug and sustained-released tablet in this paper. From the research content, the results could be concluded as follows:Preparation and evaluation for crude drug:Pretreatment condition of ziziphi spinosae semen:The saponin of ziziphi spinosae semen was taken as indexs were taken as index. The highest content of saponin was the ziziphi spinosae semen, which was 3.00mg·g-1.Extraction condition of saponins in ziziphi spinosae semen:The saponin of ziziphi spinosae semen was taken as index. Comparing the different methods to determine the optimal process, the optimum conditions of heating reflux extraction were as follows:7 of liquid-solid ratio, extraction temperature 76 ?, 70% of ethanol concentration, extraction time 2.5h, extracted 3 times by response surface methodology on the basis of single factors. Under the optimal condition, the content of saponin in ziziphi spinosae semen was 4.034 mg·g-1.Purification process saponins in ziziphi spinosae semen:The saponin of ziziphi spinosae semen was taken as index. HYA-501 maeroporous adsorption resin has high adsorbance and desorption rate, the optimum conditions were determined as follows:the sample concentration was 1.614 mg·mL-1; flow rate was 2BV·h-1; the elutive order was that the pure water 150mL,30% ethanol 50mL,70% ethanol 100mL.in the 70% ethanol, elutive rate was 2 BV·h-1. Under the optimal condition, the content of saponin in ziziphi spinosae semen was 64.2%, RSD=0.40% and the purity reached 256.7%. This method has good reproducibility.Quality evaluation for crude drug:Provision of the content of total saponin in ziziphi spinosae semen was less than 60%, the content of Jujuboside A not less than 5%. The investigation of high temperature test and high humidity test showed that the saponin in ziziphi spinosae semen as crude drug has good stability.Preliminary pharmacodynamic evaluation for crude drug:Low, medium and high dose with saponin in ziziphi spinosae semen could inhibit mice autonomic activity. It showed that saponin in ziziphi spinosae semen had hypnotic effect. In addition, it had coordinated effect of amobarbital sodium to central nervous system. It showed that saponin in ziziphi spinosae semen was the main composition of the central nervous system.Preparation and evaluation for sustained-released tablet:Prescription process about preparation:Accumulative release percentage was taken as index, the optimal formulation conditions for sedative sustained-released tablet was:crud drug was an amount of 50%, HPMC K15M was an amount of 30%, lactose was an amount of 15%, microcrystalline cellulose was an amount of 5%, and the amount of magnesium stearate was 0.5% by orthogonal experiment. Sedative sustained-released tablet was made under the optimal condition, accumulative release percentage could be achieved 37.5%?42.5% in 1h,67.5%?72.5% in 4h,87.5%?92.5% in 8h, which meet the requirements of the target tablet. Release characteristics of sedative sustained-released tablet accord with Higuchi equation. And it was conformed to non-Fickian diffusion. Therefore, release characteristics with sedative sustained-released tablet belongs to the synergy of drug diffusion and matrix erosion.Property, physical and chemical identification, weight variation, frangibility, accumulative release percentage of sedative sustained-released tablet were all meet the requirements of sustained release formulations in "Chinese Pharmacopoeia" 2015 edition. Provision of the content of saponins in ziziphi spinosae semen was less than 75mg/tablet, and Jujuboside A content was less than 5mg/tablet of sedative sustained-released tablet. High temperature test, humidity test, accelerated testing, and ongoing long-term test all showed that the sedative sustained-released tablet has good stability.The results could be concluded as follows:The extracted and purified saponin in ziziphi spinosae semen has great stability and good hypnotized effect. Hydrophilic gel matrix sustained release tablet was made with purified saponin in ziziphi spinosae semen, which has good hypnotized effect, controllable quality and good stability, and meet the requirements of pharmacopoeia.