Optimization Of The Formulation Of Quetiapine Fumarate Sustained-release Tablets And Quality Analysis

Object:The first thing was that developed methods for the determination of release,content and related substances of quetiapine fumarate by UV and HPLC, respectively.Prepare Quetiapine fumarate sustained-release tablets. By investigating the stability ofthe product under different conditions and evaluation in vitro, the formulation wasevaluated.Methods:1) Release apparatus of Quetiapine fumarate sustained-release tablets is USP I(basket), citrate as the release medium at100r/min, UV was adopted to determine theabsorbance of quetiapine at288nm. Calculated the cumulative releases of Quetiapinefumarate sustained-release tablets and Seroquel Seroquel XR to do comparison, as anevaluation method in vitro.2) An HPLC method was adopted with Agilent Zorbax Eclipse XDB-C8(25cm×4.6mm,5um). The mobile phase consisted of a mixture ofacetonitrile-methanol-0.02mol/L diammonium phosphate solution (70:540:390), withthe detection wavelength at230nm. The flow rate was1.0mL/min, Sample20uL.3) Using comprehensive score of the accumulative release rate as response value,Plackett-Burman Design was adopted to screen significance of influencing factor withwhich as independent variables and formulation of Quetiapine fumaratesustained-release tablets was optimized by CCD and response surface methodology.Results:1) Formulation consists of Quetiapine fumarate38.33%, HPMC K4M11.29%,PVP K9017.20%, sodium citrate8.00%, MCC8.00%, lactose15.14%, magnesiumstearate2.00%.2) The teste of Similarity of the tested tablet and Seroquel XR was good according to similar factors which were74,84,82,69in deionized water, ph1.2hydrochloric acid solution, ph6.8phosphate buffer, citrate solution, respectively.3) Related substances of Quetiapine fumarate sustained-release tablets whichdetected by HPLC in stability tests were that known single impurity less than0.15%,unknown single impurity less than0.15%, total impurities less than0.4%, in line withstandard requirement.Conclusion:1) The methods were feasible for the determination of in vitro release, contentand related substances of Quetiapine fumarate sustained-release tablets.2) Release behavior of the formulation which was optimized by Plackett-Burmandesign combined CCD-response surface methodology was consistent with SeroquelXR, and impurities were in line with standard requirement. So the formulation wasoptimal.