Preparation And Evaluation Of New Broad-spectrum Antiviral Drug GT844 Masked Granules

Cepharanthine(CEP)is mainly isolated from the plant Stephania cephalantha Hayata and has antiviral properties.GT844 is a new compound developed by molecular modification to simulate the structure of antiviral properties in the CEP.Pharmacodynamic experiments show that GT844 has broad-spectrum antiviral properties.As the environment of modern social contact becomes more and more complex,the antiviral drugs designed by "one drug to deal with one virus" can no longer meet the demand,which makes GT844 have broad development prospects and application space.However,earlier studies have shown that GT844 is a water-soluble bitter compound and,like most of the newly discovered compounds,has an uncomfortable taste.The taste of compounds severely restricts the use of drugs,especially for the elderly and children,as well as for critically ill patients.Improving the taste of drugs occupies a very significant position in the development of pharmaceutical preparations.This topic aims to prepare GT844 taste-masking agents and evaluate it in a series to improve GT844 taste.1.Preparation GT844/ cyclodextrin complex to form a "molecular barrier" between API and bitter taste receptors.Four different methods of preparing GT844 and cyclodextrin complex were designed,and the mask preparation was evaluated by the human taste evaluation team and the simplest and most efficient preparation method was to mix GT844 with cyclodextrin to make particles.The effects of cyclodextrin type and amount of cyclodextrin on the masking effect were screened by single factor method.The results showed that the best masking effect was hydroxypropyl-?-cyclodextrin(HP-?-CD).The optimal molar ratio of GT844 to HP-?-CD that can completely mask the bitter taste of the drug is 1:15.With the aid of ?-ASTREE electronic tongue,the effect of HP-?-CD compound particles with different molar ratios was measured,and the evaluation model of GT844/HP-?-CD compound particles was established by principal component analysis(PCA).after the validation of the model,the results are highly reliable.The optimal prescription composition was consistent with the results of the human mask evaluation team.The formation of GT844/HP-?-CD inclusion compounds was demonstrated by means of Scanning Electron Microscopy(SEM),Differential Scanning Calorimetry(DSC),and Powder Diffraction(XRDP).After the optimal prescription ratio of the molecular complex particles was washed to clarify the solution,it could completely conceal the bitter taste of the GT84 while greatly improving its taste.On the one hand because of the "molecular barrier ".On the other hand,the sweetness of the HP-?-CD itself makes the aqueous solution of GT844/HP-?-CD mask granule slightly sweet and smooth.2.Prepared GT844 taste-masking pellets that form a "physical barrier" around the APIDesign compatibility experiments of raw and auxiliary materials and screen suitable excipients.Masked granules were prepared by extrusion-circle method and evaluated by three factors: roundness,yield and dissolution.Finally,the optimum formulation of the extruded round pellets was :70% PH101,20%EC,5% PVP K30.The prescription has a certain drug dissolution lag effect,and only 11.77% GT844 released within 15 s of in vitro dissolution.Although it can hardly completely eliminate the bitter taste of the drug,it can greatly delay the production of bitter taste.All in all,on the basis of not affecting drug dissolution,the physical barrier pathway of extrusion-rolling process can reduce the bitter taste of the main drug to a certain extent,supplemented by the prescription masking technology of cyclodextrin molecular complex,which should be able to achieve GT844 ideal masking effect.