Research Felodipine Blasting Type Pulsed-release Tablets

ObjectivePerparing Pulsatile-Release Tablets of Felodipine and optimizing it’sprescription through the uniform design, to make it sure that the preparedtablets will be blast at the preset time, and can rapid release drug effectively，then quality assessment and stability investigation of the prepared pulsatile-slice will be made. Rabbits as experiment object to study that thepharmacokinetics and bioavailability in vivo of the autonomousPulsatile-Release Tablets of Felodipine by establishing a determination methodof Felodipine blood drug concentration in the body.MethodsUnderring the condition of fixed coating process parameters, it is can beinvestigated that somethings work on drug release behavior of thepulsatile-release tablets such as the composition of slice, prescription of coatingfilm, condition of drug release in vitro, supplementary material, etc, to selectsomeones that may influence in drug release behavior of the blastingpulsatile-release tablets contains expansive agent, pore-foaming agent,plasticizer and other accessories. It is made as a standard that the time spenton10%deliverance of the pulsatile-release tablets, so that we can estimate theeffection on the pulsatile-release tablets drug release deliverance with differentfactors. Optimizing the prescription craft by uniform design, to determine theaspect of tablets-autonomous like evenness of deliverance, content,homogeneity, and examine somethings related, inspect stability of sample atlast. In this study, commercially Felodipine Sustained Release Tablets as reference substance, autonomous pulsatile-release tablets as experimentalones. Establishing assay method of Felodipine blood drug concentration withconsulting some related literature and summarizing experimental experience.Feeding6healthy Big-eared Japanese rabbits autonomous pulsatile-releasetablets (standard: including dosage is5mg) and commercially FelodipineSustained Release Tablets (standard: including dosage is5mg) respectivelywhen limosis once by the means of that cross-over design between twopreparations and dicycle. Then, using HPLC method to measure bloodconcentration in different time points, describe drug-time curve in vivo, computerelated pharmacokinetics parameter through blood drug concentration eachpoint in time last.ResultsThrough the single factor investigation and uniform design to optimize thebest prescription, expansive agent in tablet core is low instead of hydroxypropylcellulose (L-HPC), content account for10%of the tablet core weight; Plasticizerneighbors in coating liquid butyl phthalate (DBP),8.5%(volume) of the EC, holeagents for PEG6000, content is7%(quantity) of the EC; Through the in vitrorelease test, preparation of pulse, delay for (4.1±0.2) h, within the lag (1.5±0.2) h, drug release cumulative drug release above90%. After the earrabbits oral medicine, measure its blood drug concentration, calculatingpharmacokinetic parameters. Reference preparation and a preparation were themain pharmacokinetic parameters are: Tmax（3.50±0.547）h，(5.667±0.516) h；Cmax(51.23±5.12) ng·mL-1,(67.865±3.810）ng·mL-1；AUC0~48(351.161±42.052)ng·h·mL-1,(382.453±31.82)ng·h·mL-1;AUC0-∞(370.051±44.082)ng·h·mL-1,(409.524±18.024) ng·h·mL-1,relative bioavailability is(110.35±10.14)%, statisticalmoment calculation of two kinds of preparations of average residence time theMRT（15.307±1.43）h、（13.488±1.63）h. ConclusionCompared Felodipine blasting type pulse preparation technology issimple, the optimized prescription to reach4h blasting design requirements,and has a good drug release behavior. Homemade sample release uniformity isgood, the content and uniformity, related substances examination conform tothe requirement of pharmacopoeia. Homemade release tablets with referencepreparations pharmacokinetic parametersCmax,Tmax,AUC0~48the bioequivalenceanalysis there are significant differences (P <0.05). The experiment of thepreparation of pulse Tmax significantly delayed, a significant rise in Cmax,according to the results of the in vivo pharmacokinetic experiment preliminaryjudgment homemade felodipine blasting type pulsed release tablets, delayedrelease drug in the body, has the obvious characteristics of drug release, timedelay and pulse effectively improve bioavailability felodipine, has reached theexpected design experiment purposes, hypertension dosage regimen for clinicaltreatment and research to provide effective reference.