Well On Behalf The Cabey Dispersible Tablets Of The Prescription Process And Quality Standards

Entecavir,a new nucleoside analogue,is a effective selective inhibitor of the replication of hepatitis B virus.It has been developed as an anti-hepatitis B virus agent for treatment of chronic hepatitis B virus infection by Bristol-Myers Squibb Company and been recently approved in US for the therapy of chronic hepatitis B.Intro this compound has be confirmed to be far more effective than other nucleoside analogue.In animal models and clinical studies,Entecavir revealed impressive reduction of serum viral DNA and excellent suppression of hepatitis B virus replication without significant side effects or evidence of toxicity.Until now,no Entecavir resistant viral mutants have been described and thus further positive response is foreseen in the future.The essay studied the formulation and preparation process,quality standard and stability of Entecavir dispersible tablets.1.Formulation and preparation process research of Entecavir dispersible tabletsConsidering the drug's dissolubility and dosage,A L₉(3⁴)orthogonal design was performed to optimize the formulation of Entecavir dispersible tablets with dispersion uniformity,friability, disaggregating time as parameter of investigation.Based on the study above,the optimal formulation was determined:61%Lactose,28%MCC,5%CMS-Na,2%HPMC.According to the results of formulation and preparation research,three batches of Entecavir dispersible tablets were produced,which the dissolution,related substances,relative content and uniformity of content of them were all conformity.The result showed that the formulation and preparation was reasonable and stable,the quality of products was controllable.2.Quality standard research of Entecavir dispersible tabletsThe quality control of Entecavir dispersible tablets was researched,which was the key work in the study.According to character of Entecavir and feature of dispersible tablet,a HPLC method was set up for differentiation of Entecavir dispersible tablets,HPLC methods were established for dissolution,related substances,relative content,and isomers analysis of it.The dissolution determination was finished with a Diamonsil C₁₈column and the mobile phase was acetonitrile-water(8:92);the related substances and relative content were determined by using a Waters C₁₈column with gradient RH-HPLC,which the mobile phase A was acetonitrile-water(3: 97),the mobile phase B was acetonitrile,the gradient procedure was 0～10 min:A 100%â†'90%; 10～15 min:A 90%;15～25 min:A 90%â†'60%;25～28 min:A 60%â†'100%;the separation of isomers of Entecavir was performed by chiral HPLC,the Daicel Chiralpak AD-H column was applied with the mobile phase consisting of absolute alcohol—n-hexane(60:40).The flow rate of these HPLC methods was 1.0 ml·min^-1and the wavelength was 254 nm,the column temperature was 30℃.Each method was exact,sensitive,had good selectivity and reproducibility while the excipients and decomposition products could be well separated from Entecavir.These showed that the analytical methods were reasonable and practical,the quality was controllable.According to three batches of experimental results,the draft quality control standard of Entecavir dispersible tablets was formulated.3.Investigation on stability of Entecavir dispersible tabletsReferencing Guidance Principle of Investigation on Drug Stability,the stability test of Entecavir dispersible tablets had been carried on stress tests which included 4700 lx strong-light test,60℃high-temperature test,RH 92.5%high- humidity test by inspection of the character,dissolution, related substances,content examination,optics-purity and so on.At the same time,an acceleration test and a long time normal condition stability test were also carried on.These results indicated that Entecavir dispersible tablets were stable,nearly without any quality changes during the stability study.The preparation procedure and the draft quality control standard were reasonable and feasible.