Felodipine Sustained Release Tablets And Animal Pharmacokinetic Study

Felodipine (felodipine, FL) is a highly vascular selective calciumantagonist developed by AstraZeneca of Swedish, is mainly used to treat avariety of essential hypertension. Felodipine conventional tablets oral hasblood concentration peak and valley phenomenon, and the administrationfrequently, so it made a sustained-release formulations, there has someadvantages,such as easy to take, the less frequent administration, lessadverse reactions, etc.The main content of this paper is:(1) the establishment of in vitrorelease determination method;(2) to prescription screening and preparationprocess of felodipine sustained-release tablets;(3) establish method fordetermination of felodipine and related substances;(4) research stability offelodipine sustained release tablets;(5) preliminary pharmacokineticsresearch in beagle dogs body dynamics of felodipine Sustained ReleaseTablets.Established two method (UV and HPLC) to determin the sample of invitro release. Respectively, the results of method validation were in line withthe requirements of the methodological research, and the measurement was no significant difference in every sample. Taking into account the limitedand simplicity of the experimental conditions, we select UV method for thedetermination of the release of this product.Felodipine tablets were prepared by direct tabletting method. Therelease rate was choosed as an indicator for the single factor explorationabout the specifications and the amount of HPMC, lactose dosage, pressureand felodipine particle size, and optimized by orthogonal methodology.Adjust the prescription to fit the requirements of every point of in vitrorelease. Determination of content uniformity, The comparison about in vitrorelease behavior from test products with commercially available products,the results shows that the similar factor was greater than50in the differentrelease media, the f2is and basic acquaintance.The behaviors of testproducts and commercially available products in release media were allfitting the Retrer-Peppas model. The mechanic of drug release wassynergistic action about diffusion with skeleton dissolution.Establish a HPLC method for determination of felodipine and relatedsubstances, the detection wavelength was362nm and254nm. Felodipine in2μg/ml~32μg/ml the concentration within a good linear relationship witharea, known impurities Ⅰ showed a good linear relationship in0.2μg/ml~4.0μg/ml concentration range, recovery, precision and stability meet therequired.Reference to the “the chemical drug stability guiding principles”, the test on influencing factors and accelerated stability of felodipine sustainedrelease tablets had been done. Felodipine is unstable in light and hightemperature, so it should be stored in dark and at room temperature.Accelerated test at40℃±2℃shows that the related substances of felodipinewould increase after placed in a long time under high temperature conditions,but its compliant range to meet the production and storage requirements.The auto-control crossing trial design had been used forpharmacokinetics research of test products and commercially availableproducts in Beagle dogs. The plasma concentration of felodipine wasmeasured by HPLC method. The data calculated by DAS2.1.1software, therelative bioavailability of the test products was94.7%of the commerciallyavailable products. The confidence interval is72.8%~125.8%. There was nosignificant difference between the test products with commercially availableproducts in tmax, Cmax, AUC, t1/2.So we predict the test products similar to thein vivo pharmacokinetic characteristics of commercially available products.By in vitro and in vivo evaluation of known absorption of the percentage ofin vitro release of a good correlation for Felodipine sustained-releasetablets.