The Research Of Fucoidan Sustained-release Tablets

Fucoidan is a marine polysaccharide mainly derived from brown algae.Fucoidan has diverse pharmacological activities including anticoagulate and procoagulate,antioxidant,antiinflammatory,hypolipidemic,antiviral,antitumor and immunoregulatory effects.Currently,there is only one fucoidan-based drug in China,namely Haikun Shenxi capsule(approved number Z20030052).The drug is widely used in clinical treatment of chronic renal failure and uremia.However,this drug has only capsule form,which can't meet the growing needs in the market.Therefore,the development of new sustained-release formulations based on its chemical properties is of great significance to broaden the clinical applications of this drug.Based on the above research purposes,we first characterized the chemical properties of fucoidan used in our present research.The molecular weight was determined to be 2.271×105Da by high performance gel permeation chromatography and multi-angle laser scatterometer.The composition of the monosaccharide was determined by 1-phenyl-3-methyl-5-pyrazolone(PMP)method coupled with high performance liquid chromatography.The molar ratio of the monosaccharide in fucoidan Mannose(Man): Glucosamine(GlcN): Rhamnose(Rha): Glucuronic acid(GlcA): Glucose(Glc): Galactose(Gal): Xylose(Xyl): Fucose(Fuc)= 0.08: 0.02: 0.03: 0.08: 0.04: 0.16: 0.02: 0.56.The optimum preparation process of fucoidan sustained-release tablets was studied and determined by comparing three methods namely,powder granulation,wet granulation and melting granulation.Our results indicate that wet granulation was the best method for the preparation of fucoidan sustained-release tablets.To optimize the best compositional ingredient of the sustained-release tablets,the orthogonal design experiment and the response surface design experiment were respectively conducted.The optimal ingredient for the preparation of sustained-release tablets was as follows: fucoidan for 41%,HPMC-K4 M for 20%,CMC-Na for 20%,octadecanol for 13%,lactose tablets for 5% and magnesium stearate for 1%.During the in vitro study of the sustained-release tablets,the release uniformity was found to be consistent within batch and inter-batch investigations.The cumulative release value of the active drug was 32%,64% and 92% respectively in the 2h,6h and 12 h.The in vitro release of the sustained-release tablets in simulated artificial gastric juice and intestinal juice showed that the tablets could stay stable in the artificial gastric juice and have sustained release effect in the weak alkaline environment of simulated small intestinal fluid.In vitro release model was analyzed by using Origin 9.1 software.The release kinetics model of the sustained release tablets was found to be a first-order release model by comparing zero-level release,primary release,Higuchi release and Ritger-Peppas release,which has distinct release characteristics.Based on this,the release mechanism was further invesitgated using the Ritger-Peppas model.We found that in this model,n=0.6015(0.45 < n < 0.89).This indicated that Fick diffusion and skeleton dissolution diffusion act together to release the drug in fucoidan sustained-release tablets.Finally,the appearance standard,identification method,examination mehod,content determination protocol and in vitro release performance of the sustained-release tablets were studied.Besides,the quality standard of fucoidan sustained-release tablets was also established.Our data demonstrated that three batches of different sustained-release tablets are in line with the requirements of Chinese Pharmacopoeia(2015 Edition).These results provide a theoretical basis for the production of fucoidan sustained release tablets.In summary,the preparation method of fucoidan sustained-release tablets,the effect of excipients on the release of drugs and the optimization of the compositional ingredients of the tablets were systematically studied.The fucoidan sustained-release tablets were successfully prepared.Our data illustrated that the drug release behavior of the tablets is line with the first-order release pattern and the drug is released driven by a combination of Fick diffusion and skeletal dissolution effects.In addition,the standard for the quality control of fucoidan sustained-release tablets was established using UV spectrophotometry,which is applicable to study the in vitro release of fucoidan sustained-release tablets.Collectively,our study provides a theoretical basis for the development and application of sustained-release formulations of fucoidan and other marine polysaccharides.