Study On The Controlled Released Tablets Of Doxazosin Mesylate

Complication of Hypertension and Benign Prostatic Hyperlasia is a common disease in elderly patients.Doxazosin mesylate,as a first-line drug to treat this complication,has not been widly developed at home and abroad.Compared to ordinary tablets,the advantage of doxazosin mesylate sustained-release prepration is that it can effectively reduce the"first dose" effect,which can result in the upright postural dizziness,and reduce the adverse recations and the delivery times.It can also improve the compliance.The High-performance liquid chromatography(HPLC)method was established for investigating the content of DOX in the intestinal absorption experimental samples.The Single-pass perfusion method was adopted for the rat's in vivo intestinal absorption test.In this experiment,the influences of different drug concentration,perfusion rate and the absorption site was investigated.And we choose gravimetric method to calculate the absorption rate constant(Ka)and the apparent absorption coefficient(Papp).Through one-way ANOVA test by SPSS 17.0 statistical software,the results of this experiment showed that:perfusion rate could significantly affect Ka and Papp.Drug concentration had little effects on Ka and Papp.Ka and Papp values of jejunum and ileum were not significant different.However,the absorptipon values between the top of small intestine(doudenum)and the colon are significant different.However,the Papp of DOX in colon and small intestine are bigger than 1.2*10-3 cm/min,so that the DOX could be easily absorbed throughout the general intestine,and the DOX is suitable to be designed as a kind of sustained-release tablet.In this paper,the effects of many factors including different viscosities of HPMC,different contents of HPMC and tartaric acid,was investigated by single-factors method.Draw support from orthogonal experiment design,the best formulation and preparation technique was optimized.Get fitting to the release behavior of commercial tablet(Pfizer(?)),the result of similar factor method(f2)showed that the best formulation tablet had the similar in vitro release behavior.We got the release curve fitting to the different mechanism,and used the correlation coefficient to test,and finally got the result which showed that the drug release behavior is mainly due to skeleton dissolution,and meet the zero-order release process.Lastly,in order to inspect that if the best formulation could be used in industrial production,we made the scale-up production.The result showed that the reproducibility between three batches of preparation is good,the technology is feasible.The pre-release are rapid,so that we need to futher adjust the prescription process.