New Prepatation Technology Research And Apply Of Duloxetine Hydrochloride Enteric-coated Tablets

Duloxetine hydrochloride is a new listing of a selective5-serotoninand noradrenaline-reuptake inhibitor (SNRIs). It is indicated for thetreatment of major depressive disorder, as well as a number of other dieases.Duloxetine hydrochloride is unstable in acidic environment, and prone todegradation, so we need to improve the technology and quality standard ofdomestic preparation and develop30mg preparation which is much-needed onclinic urgently. In order to reduce adverse reactions of gastrointestinalagents, there is need to develop sustained-release formulations.This project used new melting granulation technology to avoid contactingwith water and organic solvents in the granulation process and filter outaccessories which is suitable for immediate-release tablets. Theprescription was composed by main drug, sucrose, polyethylene glycol6000,microcrystalline cellulose and cross-linked povidone. We optimized the meltgranulation process parameters, while optimizing the isolation layer coatingliquid prescription. Add the controling on1-naphthol, the largestdegradation product of hydrochloride preparation, to the quality standards.The limitation of item "related substances" reduced from1.5%to1.0%, and enhanced the precision and accuracy of the test method so as to achieve thequality standards upgrading. By stability, process validation and amplifiedpilot scale showed that Duloxetine hydrochloride30mg enteric-coatedimmediate-release tablets prescription designed reasonably, technologyoperated handy, improved the product release rate and stability and was goodfor industrial production. We analysised the pre-test data of human bloodconcentration of amplified pilot scale samples and evaluated the release ratein vitro and the absorption in vivo preliminarily. The results was indicatedthat the relative bioavailability was118.3%.The new melt granulation technology, choosing the water-soluble hot meltmaterial and hydrophobic hot melt material ratio, prepared Duloxetinehydrochloride enteric-coated sustained-release tablets successfully. Theprescription was composed by main drug, polyethylene glycol6000, sucroseand stearic acid. Through artificial gastric juice, the core release lessthan40%of the labeled amount after one hour, and release more than70%ofthe labeled amount after four hours in pH6.8phosphate buffer solution, sothat it can extend the releasing time of Duloxetine hydrochloride in theintestinal tract appropriately. The results showed that Duloxetinehydrochloride in this preparation had less degradation, more stability.