Study Report On Demolition And Enteric-coated Potassium Sodium Dehydroandroan Drographolide Succinate Pellets

Potassium Sodium Dehydroandroan drographolide Succinate (PSDS) is a traditional chinese medicine extracted from Andrographis, the main component is potassium sodium dehydroandroan drographolide succinate. It is widely used for viral pneumonia and viral upper respiratory tract infection treatment in clinical. Nowadays, there is only PSDS freeze-dried powder for injection, it has many side effects and is inconvenient to use. PSDS as a neutral drug is unstable in acidic and alkaline conditions, the normal oral preparations can easily be damaged by gastric acid, not completely absorbed and the bioavailability is low. The enteric-coat pellets of PSDS can be expected to have good absorption for the reason of avoiding destruction in gastrointestinal tract.Firstly, the absorption kinetics was obtained by the in situ perfusion method in rats and phenol red was used as reference solution. The absorption of different concentrations of PSDS in the intestine was investigated by HPLC. Experimental results showed that the Ka value of PSDS was the largest in low concentration, if made of small dose of oral preparation, repeated dosing, and PSDS had a larger absorption rate to ensure the efficacy and reduce adverse reactions. The Ka value of PSDS was larger in jejunum than in duodenum and the absorption rate was equal. Through the experiment proves, if made of jejunum on colon-specific delivery of enteric preparation, to better play its therapeutic effects.Secondly, we established the determination method for the concent of the pellets and the release rate in vitro. We made pill cores containing PSDS by extrusion - spheronization method, and investigated the process factors such as extrusion speed, spheronization speed, spheronization time and the prescriptin factors such as bulkin agents, adhesives, the type and amount of disintegrating agents. Orthogonal design was used to optimize prescription composition and preparation process, through the reproducibility test to validate the prescription rationality and preparation process stability. By using ethyl cellulose and Eudragit L with different mixture ratios as coating material, adding proper amount of plasticizer, in vitro as evaluation indexes, by adjusting the coating thickness, preparation and quality to meet the requirements of PSDS enteric coated pellets.The results showed that using ultraviolet spectrophotometry to determine the content and release of PSDS pellets is simple, sensitive and highly specific. In single factor test based on orthogonal experiment for optimization of cores, the best prescription composition and preparation process is:PSDS:MCC:SiO2=7:7:5, extrusion speed:1080 rpm, spheronization speed:960 rpm, spheronization time:5min, EC:Eudragit L=35:65, plasticizer:1.71%, coating weight gain:5%.The release of PSDS enteric-coated pellets in the artificial gastric juice (pH 1.0) was less than 10%, while in artificial intestinal fluid (pH 6.8) was more than 80% in two hours. The release of PSDS enteric-coated pellets accorded with the regulations on the release rate of sustained release preparation in ChP.Finally, we established a method to determine the concentrations of PSDS in the plasma and the intestinal content of small intestine of rats. A single oral dose given intragastrically on enteric coated pellets (equivalent to 80mg/kg containing PSDS), respectively, given medicine before and after administration of 1,2,2.5,3, 3.5,4,5,6,8h from the carotid sinus blood, determination of rat plasma drug concentration of PSDS and by DAS2.0 drug dynamics program for kinetic parameters. In medication after 2,4,6,8h breaking the neck to death rat, along the ventral midline cut, complete removal of small intestinal segments and colon segment, sectional anatomy and record the number of pellets, and determinate the content of PSDS content. The results showed that the determination of the plasma concentrations of PSDS by HPLC is simple, sensitive and specific. The drug was detected after two and a half hours, it suggested that PSDS enteric-coated pellets could be absorbed in rats after oral administration. The peak concentration reached to 3.02μg/ml after 5 hours, The main pharmacokinetic parameters:t1/2 2.69 h, Tmax 5 h, Cmax 3.02μg/mL, the area under the plasma concentration time curve was 6.42 g.h.mL-1.In fasted rats under the state test, after intragastric administration of 2h pellets were mainly distributed in the stomach; 4h mainly in the small intestine, small amount of distribution in large intestine; 6h 1/2 pellets in large intestine,1/ 2 of the pellets in the small intestine; 8h pelletswere mostly in large intestine, Partial discharges in vitro, compared with the rat plasma concentration determination results,further proof of the drug after oral administration in rats intestine positioning release characteristics.Conclusion:PSDS pill core loading larger drug could be prepared by extrusion-spheronization method,by fluidized bed coating preparation of PSDS enteric coated pellets, this method is feasible and suitable for industrialized production; Rats in vivo tests confirmed, PSDS enteric coated pellets has a certain absorption in the small intestine, it is feasible to prepare PSDS for oral administration.