Study On Solid Sustained-Release Dosage Forms Of TSFG

Ginseng was very famous herb in the traditional Chinese medicine . In this thesis, TSFG(Total Saponins of Folium Ginseng) was selected as the model drug. In order to probe the way-out and feasibility for new controlled-release dosage forms, the sustained-release matrix tablets and sustained-release pellets of TSFG was made.Total saponins contents of TSFG and its preparation was determined by UV, ginsenoside Rgi and Re by HPLC at the same time which the method was introduced for the first time. Cumulative release percent in sustained-release preparation of TSFG was attained by HPLC for determining the contents of ginsenoside Re(including Rg1).The combined matrice consists of HPMC, EC and lactose. TSFG and excipients was blended and manufactured into tablets by direct compression procedure or wettest granulation method in accordance with such experimental design methods as uniform design or orthogonal design. Appling Peppas equation,MDT(mean dissolution time) and f2(similarity factor) to evaluate the drug release behavior of ginsenoside Re(including Rg1) in this combined matrix systems. The factors influencing drug release such as the content and properties of matrix components and SA/Vol of the tablets was studied. The drug release behavior was influenced remarkably by SA/Volof the tablets and a new Peppas equation was intruduced for the first time.Suited proportion of MCC, lactose and TSFG was confirmed and appling appropriate concentration ethanol to wet the blending of TSFG and excipients, then TSFG pellets was manufactured by extrusion-spheronization. By means of orthogonal design and the way to evaluate the pellets, preparation conditions was confirmed.Appling sphericity of roundness and percent of yield as main index, the effect of different amounts and concentration of granulating liquid, extrusion speed, spheronization speed and spheronization time were investigated. Appling planar critical angle, repose angle, size distribution, bulk density, friability, flow rate and yield percent to evaluate the quality of pellets, the pellets formulation was optimized by means of orthogonal design. The dissolution test indicated uncoated pellets dissolved in 30 minutes.Using fluid bed coating equipment, the pellets coated with organic solvent-based EC solutions or aqueous acrylic polymers dispertions such as EC ethanol solution, Surelease and Eudragit NE 30D. Effect of formulation and technology factors on drug release were investigated and above all the coating polymers controlled drug release effectively and reasonably. The effect of amount of poremakers and coating levels on drug release was remarkably. By means of uniform design and according to the results of dissolution test, the optimal coating formulation was confirmed and the release of ginsenoside Re(including Rg1) from the coated pellets was sustained and perfect.Absorption kinetics of ginsenoside Re(including Rg1) in the small intestine was investigated using in siln perfusion method in rats, it was showed that ginsenoside Re(including Rg1) absorbed very quickly, but very incompletely. Both in rats and dogs, the concentration-time curves of ginsenoside Rg1 and Re fit in two-compartment model after oral administrating a large dosage of TSFG. Original drugs were determined within 30 minutes and Tmax was 35 minutes in rats, 55 minutes in dogs.The plasma concentration of ginsenoside Rg1 and Re in three healthy dogs after oral administration of sustained-release pellets of TSFG was studied with TSFG as a reference preparation. The concentration-time curves of ginsenoside Rg1 and Re was milder very much than TSFG's. Compared with TSFG, the relative bioavailiability of coats sustained-release pellets was 110%, Tmax and mean residence time(MRT) prolonged remarkbly, while Cmax decreased greatly.