| Terazosin hydrochloride(terazosin hydrochloride),the chemical name is 1-(4-ami no-6,7-two methoxy-2-quinazoline based-4-[(-2-)tetrahydrofuran formyl piperazine hydrochloride hydrate)two,is the analogue of prazosin,developed by American Abbot company,started for clinical in 1985,is a synapse after adrenergic receptor blockers.It can expand blood vessels and reduce peripheral vascular resistance,so as to reduce bl ood pressure and relax bladder neck and prostate capsule.It has a significant relieving effect on prostatic hypertrophy symptoms.Due to its good clinical performance,it was approved by FDA in 1987 for the treatment of hypertension.After being recommended by the American Urological Association,clinicians used it as the first choice for the t reatment of benign prostatic hypertrophy in 1992.Terazosin hydrochloride in China has been listed,has been used in the treatment of mild to moderate hypertension and beni gn prostatic hypertrophy,characteristic is not influenced by food,good oral absorption,high bioavailability in the human body,the efficacy of longer duration,the half-life is 2～3 times of prazosin,achieved good clinical efficacy.There are two types of trazosin hydrochloride in China:tablets and capsules.Because th e drug to dilate blood vessels,antihypertensive effect quickly,patients according to convention al doses can produce first dose effect,headache,dizziness,weakness,palpitation,nausea,ortho static hypotension,and so usually require patients taking the first dosage is on the first day of sl eep before the meal 1 mg,in order to prevent and reduce the patients the first dose effect and th e occurrence of syncope,after identifying patients without obvious physical discomfort,you ca n slowly increase the dosage,after discontinuation of treatment need to be restarted,must grad ually increase the dose from 1mg to achieve regular dose.The oral dose of tablets and capsule s are difficult to accurately grasp the patients,this study focuses on the issue,in order to reduc e the effect of the first dose of medicine,improve patient compliance,modern pharmaceutical p reparation technology of terazosin hydrochloride controlled-release tablets for use,preparatio n technology and quality standard research.This study first use of domestic terazosin hydrochl oride raw material and hydroxypropyl methyl cellulose HPMC and pre gelatinized starch,mad e of hydrophilic matrix tablets using film coating technology to improve the control of drug rel ease rate,ethyl cellulose EC as membrane material,polyethylene glycol PEG6000 as plasticize r,sodium chloride NaCl as porogen finally,made the membrane controlled release matrix table ts.On the basis of single factor investigation,L9(3)Iorthogonal design was used to optimize th e best prescription and technology,and the stability and feasibility of the formulation technolog y were verified scientifically and systematically.According to "People’s Republic of China Pha rmacopoeia" 2015 edition fourth principles 9013 controlled release and delayed release prepara tion of the guiding principle,with release rate as the index,according to the "People’s Republi c of China Pharmacopoeia" 2015 edition fourth principles 0931 dissolution and release determi nation method of second in different time at different prescription drug cumulative release amo unt of objects check experiment design to meet the needs of the statistical treatment,the drug r elease process of selected 3 sampling time of three time points 2h,12h,22h in vitro cumulativ e release rate as the evaluation index,analysis of variance using weighted scoring method to de termine the optimal prescription.Three batches of samples were prepared according to the pref erred prescription,and the reproducibility of the prescription and process was investigated.2 h,4h,8h,12h,18h,24h,6 times the cumulative release rate of drug release curve drawing,cal culation of three batches of similar factor f2 as the evaluation index,the results of three batche s of sample f2values were greater than 50,showed no significant difference between the thre e batches of samples is reasonable,stable process.Then,different equations were used to fit th e three batches of samples in vitro.The experimental data showed that the maximum correlatio n coefficient and the minimum mean square error were zero order kinetics equation,so as to co nfirm that the controlled release preparation was in line with zero order release.Finally,the study of quality standards is carried out.Quality standard reference "People’s Republic of China" Pharmacopoeia 2015 edition second Terazosin Hydrochloride Tablets,t o study the quality standard of the preparation of terazosin hydrochloride controlled release tab lets quality standard draft,including character,identification,related substances,dissolution,co ntent determination.Method for determination of content and related substances by HPLC of te razosin hydrochloride controlledrelease tablets,was studied,the chromatographic conditions i n research on the method of screening,research,destruction test,properties of solution stabilit y research,linear test,recovery test,repeatability test rate the method of content and related su bstances have been identified in the intermediate precision test,the system methodology of exp erimental research,and ultimately determine the detection method of related substances and co ntent.Results:within 24 hours of the sample was stable and good,show that the method is spec ific,determination of content in 0.802 μg/ml～80.20 μg/ml within the linear range between th e concentration and peak area is good,the average recovery rate(%)=99.74%,RSD(%)=0.59%,indicating the accuracy of the method is good.Based on the above test and research,comb ined with the relevant provisions of the four general provisions of the Chinese Pharmacopoei a 2015 edition,the quality standard of terazosin hydrochloride controlled-release tablets was fo rmulated. |
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