Development Of Compound Shishengbianlei Colon Targeted Capsule Based On The Compatibility Of Gentianopsis Paludosa And Sophora Alopecuroides L

Objectives: The Tibetan medicine Gentianopsis paludosa and Sophora alopecuroides were used as materials for the research on the compound prescription.Reasonable optimization of the extraction process,screen of the preparation technology,determination the quality standard of the preparation,simulating stability of different gastrointestinal environment were carried out to develop a colonic targeted capsule for clinical treatment of ulcerative colitis.Methods: Under the fixed ratio of 20:0.9(Gentianopsis paludosa : Sophora alopecuroides),the content of luteolin,Ligusticum japonicum,Ligusticum japonicum were determined by HPLC method with drawing the standard curve.Three-factor and three-level orthogonal was designed by "extraction time,extraction times,the amount of solvent".The optimum extraction parameters were optimized and verified again in accordance with the best process;Remove the alcohol from alcohol extract to no alcohol taste.Diluted with water into the water extract.The pellets core were prepared by means of a centrifugal pelletizer using starch and MCC accessories.The pellets were coated with water extract and calcified pectin solution containing certain HPMC successively by means of bottom-jet fluid bed granulating and coating technology.After being coated,the pellets obtained were filled into enteric capsules.The release of the formulation in different environments was judged by simulating gastric juice,small intestinal fluid and colonic fluid.By means of HPLC,the content of the related substances was quantified by taking luteolin as the index.TLC method was used to qualitatively determine the thin layer chromatographic characteristics of the compound targeted capsule.The stability and reliability of the preparation were confirmed by studying influence factors(high temperature,high humidity,strong light),accelerated stability test and long-term stability test of compound Shishengbianlei colon targeted capsule according to the2015 version of the Chinese Pharmacopoeia.Results: According to the results of the orthogonal test,the optimum extraction conditions were 8 times 75% ethanol,extracting twice,90min/time.Preparation of the pill: medicinal starch and MCC ratio(3:1),with water(dosage 2.1%)as a binder.The blank-pellets(40-60mesh)were rounded,smooth,uniform with material balance ? 98%;Preparation of mini-pellets: Using bottom-jet fluidized bed granulation coating machine,the concentration of water extract was kept of 1.2-1.7 g/m L(equivalent to the original dose)with adhesion better.Extract fluid flow 1.0-1.5 m L/min.Atomization pressure 0.4-0.5 Mpa.Spray speed 3.0-21 Hz.Inlet air temperature was maintained at 55?-70?,outlet air temperature 36.7?-45.5? and the material temperature were 34.4 ? to 44.4 ?.The outer layer was coated by calcium pectin solution containing 5% HPMC to enlarge the diameter of the pellets by 10%.The particle size of the obtained pellets were 0.8-1.0mm with smooth,round and uniform.With the release of luteolin as an index,neither significant release of the compound capsules was found in the simulated gastric juice for 2 hours nor release after 2 hours in the simulated intestinal fluid.The dissolution rate in the simulated colonic fluid for 1 hour reached 85.3 %and after 2 h to reach 95.3%.In the light of the new pharmacopoeia,the stability and reliability of the preparation were confirmed by studying the effects of compound capsule on the influencing factors(high temperature,high humidity,strong light),accelerated stability test and long-term stability test.Conclusions: The results showed that the extraction technology of compound shishengbianlei targeted capsule has a wide range of applications and the extraction solvent was wide used.The preparation process was highly operational and the source of the excipients was common.The results showed that colon-targeted release performance to meet the requirements of the parameters.Quality standards was easy to implement,to meet and ensure the minimum quality requirements of the preparation.Under certain temperature and humidity and light intensity range,the stability of the preparation was better.