Study On Preparation Of Mesalamine Extended-release Enteric Pellets

Ulcerative colitis?UC?is a common and nonspecific chronic inflammatory disease,which is caused by colonic mucosa.The pathogenesis of this disease is unknown.It has been listed as one of the most difficult diseases in the world by WHO.Mesalazine,as a first-line treatment for the treatment of mild to moderate active UC,must be prototype in the intestine and lesion site mucosal contact can play an effective therapeutic effect.Therefore,it usually formulated as a colon-targeted delivery formulation.At present,the mesalazine preparations on the domestic market are tablets,granules,suppositories,and capsules,most of which need multiple administrations on the day.Only one product,a product marketed by Salix Pharmas under the trade name Apriso^TM,is 375 mg once daily.The study will be prepared mesalazine sustained-release pellets,in order to develop a product that the quality and efficacy are the same with reference formulation.The study established a HPLC method for the determination of the release of mesalamine extended-release enteric pellets and content.The methods had good specificity and precision.In this paper,the basic physical and chemical properties of mesalazine were studied,including pH-solubility determination,hygroscopicity test,crystal form and particle size.The reverse-engineering was used to analyze and obtain the preparation process and the amount of auxiliary materials of the reference preparation.In this paper,Mesalazine extended-release matrix cores were prepared by extrusion-spheronization method with microcrystalline cellulose as filler,Eudragit^?NE30D as matrix material and HPMC K4M as binder.The quality of pellets mainly through roundness,angle of repose,bulk density,friability and yield as the index of investigation.This study examines the different process factors on the pellet quality and optimize the process parameters by orthogonal experimental method.The optimal process parameters ormulation was as follow as extrusion speed 30 r·min^-1,rolling speed 700 r·min^-1,spheronization time 15 min.Release,as an indicator,filter matrix pellets prescription and get the best prescription.This study fluidized bed coating technique was applied to prepare the extended-release enteric pellets.Mesalazine extended-release enteric pellets were prepared by using Eudragit^?S100 and Eudragit^?L100 as coating material,triethyl citrate as a plasticizer and talc as anti-adhesive.Investigated coating weight,the impact of the mixing ratio of Eudragit^?S100 and Eudragit^?L100 on release of extended-release enteric pellets.Also investigated the coating process parameters.The results showed that the ratio of a combination of Eudragit^?S100 and Eudragit^?L100 was 2:3,and weight gain was 14%.The study was based on Apriso^TM as a reference.f₂calculated as an indicator to compare four kinds of different media pH dissolution profile.The results showed,f₂>50,self-made pellets compared with the reference formulation in the four media release were similar.The stability investigation showed that extended-release enteric pellets are stable at high temperature.But it is more sensitive to humidity and light conditions,so prompt products should pay attention to dark and moisture-proof preservation.By fitting the release data of the mesalazine extended-release enteric pellets,the fitting results show that the equations fitted by the First order model and the Ritger-Peppas model have the best correlation.Which proves that the release process of mesalazine extended-release enteric pellets is the process of diffusion and dissolution synergy.