Study On The Preparation Technology And Quality Evaluation Of The Cilnidipine Sustained-release Tablets

Cilnidipine as antihypertensive drugs listed in1995, Fujirebio, rishita, NipponBoehringer Ingelheim, the company developed the third generation1.4-twodihydropyridine calcium channel antagonist, is one of the best drugs currently in clinicaltreatment of hypertension and angina pectoris, listed specifications tablet5mg and tablet10mg, white film. Cilnidipine effect better, but cilnidipine tablets orally two hours afterthe blood concentration peak and valley phenomenon obviously, resulting in easy toproduce first dose effect in clinical use, which were originally used, blood pressuredropped substantially, causing discomfort and side effects of cardiovascular system, sothis paper consider the drug release preparation, in order to improve the safety andeffectiveness of drugs, reduce side effects, to achieve long-term stable blood pressure,improve patient compliance. In the domestic, have developed the tablets and capsules,has not yet been developed slowly release preparations.This paper firstly established the ultraviolet spectrophotometry for cilnidipinetablets solubility determination, HPLC method for the determination of cilnidipinetablets were investigated with cilnidipine; solubility in various solvents as well as in thedissolution medium and stability (37℃), the results show cilnidipine in methanol,ethanol, slightly soluble in acetone, chloroform, soluble, insoluble in water; soluble inglacial acetic acid, insoluble in distilled water, pH6.8phosphate buffer solution, pH1.2HCl three solutions of different release medium, so need to above dissolving mediumrespectively.0.1%_Twain80, and ultimately determine the dissolving medium.Based on the sufficient investigation of drugs and various auxiliary materialsproperties, prepared by PEG6000nisoldipine solid dispersion, using microcrystallinecellulose (MCC), lactose, hydroxypropyl methyl cellulose (HPMC), cross-linkedsodium carboxymethyl cellulose (CCNa), magnesium stearate as auxiliary materials,preparation of cilnidipine tablet (Cilnidipine sustained-release tablets). From the soliddispersion preparation technology and prescription, sustained release tablets, in vitrorelease conditions were studied to control the release behavior of cilnidipine tablets. Based on the screening of single factor investigation and factors, and the formulationwas optimized by orthogonal test preparation process and system. The results show,cilnidipine sustained release matrix tablets in vitro release curves accord with theHiguchi equation. The result showed that the formulation and preparation process wasreasonable and stable.For the control of cilnidipine tablet quality, according to the physicochemicalproperties of cilnidipine and sustained release tablets preparation characteristics,established the product release, content, method for determination of related substances.The results show the method is accurate and reliable, and can effectively control thequality of the product, provide a basis for the formulation of quality standard of thispreparation. The reference drug stability experiment of the requirements, the appearance,content, related substances, the release of such items as the index, of cilnidipine tabletby influencing factor test (4500l light, high temperature of60℃and RH92.5%highhumidity) and accelerated test. Test results show that, cilnidipine in packaging theindex in the experiment process were not changed, prove that the preparation has goodstability, the preparation of studies and quality standard of reasonable, feasible method.