| The paper adopted HPMC and acrylic acid-III-resin as the basic matrix material, lactose as the exclpient. The Ketoprofen (KPF) sustained-release tablet was prepared which could release twenty-four hours continously . The dertermination method of release of it in artificial intestines fluid was set up and methodology review was made. The paper studied the factors which influence the release of Ketoprofen sustained - release tablet,optimized the Ketoprofen sustained - release tablet prescrption by uniformity design method,got the quantitative equation which expressed the Influence of the HPMC, acrylic acid-III-resin,and lactose for the release of Ketoprofen from the tablet. The equation indicates that HPMC block the release of Ketoprofen and tween-80 and lactose promotes he release. The release velocity could be adjusted by altering the ratio of the three factors in the prescription. The release experiment of the optimized prescription verified that the Ketoprofen release fitted the estimation. The three tablet samples were produced by the optimized prescnptlon, the release velocity of the three samples was stable.The determination method of Ketoprofen content in the Ketoprofen sustained-release tablet was set up by UV method and the UV method was evaluated; The release law of Ketoprofen sustained - release tablet in the artificial intestines fluid was studied initially,the Ritger-Peppas equation describes the law better.The release law of Ketoprofen sustained-release tablet in the artificial intestines fluid was the coupled action of the Pick diffusion and the gel matrix erosion mechanism and the erosion had the bigger ratio. The quality evaluation study of Ketoprofen sustained-release tablet was made and the major influencing the stability of Ketoprofen sustained-release tablet was studied. The results indicated that the tablet was stable to humidity,was sensitive to light and heat.One year accelerated test suggested that notoginseng saponins was almosdy stable.The result showed that the Ketoprofen sustained-release tablet should be packed to prevent from the light and should be preserved under low temperature.The HPLC method which determinates the Ketoprofen concentration in the human plasma and could satisfy the need of bioavailability study in the human was established and the method was certificated. As the Ketoprofen sustained-release tablet of 12 hours being the reference preparation, the bioavailability study of Ketoprofen sustained - release tablet in the human and the bioequivalence evaltion were made by two preparations two cycles crossing trial design. The results of the bioavailability trial in the human indicate that Ketoprofen absorption in the human fits the one-compartment,and Ketoprofen can be detected in the plasma within 30hours after human taking Ketoprofen orally. After single dose (200mg/tablet,l tablet at a time) ,Cmax is 5.78 1.11 g/ml, Tmax is 3.87 0.55h, AUCO-T is 38.94 9.15( g/ml)*h, MRTO-T is10.59 0.94 h. After multiple dose(one tablet daily, lasting 6 days),Ccav is 1.60 0.34 g/ml,Cssmax is 7.21 1.65 g/ml, Cssmin is 0.66 0.22 g/ml, Tssmaxis3.19 0.57h, AUC0..is 38.29 8.11 (w g/ml)*h, t1/2is 8.67 3.77h, MRTO- T is 10.66 1.27h. While sustained -release tablet comparing to the referencepreparation,its Cmax(Cssmax) decreases,Tmax (Tssmax)increases,MRT prolongs and it has sustained features; Ketoprofen sustained-release tablet and the reference preparation are bioequivalent for the AUC,its relative bioavailability of single dose is 105.10 % 30.09% and its relative bioavailability of multiple dose is 103.76 % 33.53%.The results of the bioavailability study in the human indicate that the Ketoprofen sustained-release tablet retention time prolongs, the release decreases and the purpose of once daily designed by the research was achieved.In vivo-in vitro correlation (FVIVC) of the Ketoprofen sustained-release tablet which could release twenty-four hours continously was studied. The significant regression equation between the in vivo absorption and the in... |
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