The Studies On The Floating Sustained-release Capsule Of Bifendate

Background and objective : Gastric floating sustained-release preparation is made by hydromechanical balanceable theory, after taking it orally,it can float on the gastric juice.Floating system may float in the stomach for a long time and not be influenced by the velocity of gastric emptying.At the same time,the medicament releases slowly by the anticipative velocity from the system.After the medicament released, the remnant system was emptied from the stomach.In order to prolong the time medicament staying and floating in stomach,its density must be under the gastric juice,1mg·ml^-1.The forms of Gastric floating sustained-release preparation have several types:floating tablet,floating capsule,micro- granule and micropellet.In this thesis,we prepared floating sustained-release capsule using bifendate(DDE)as the model drug.We studied the formula technology according to the results of the preliminary test;the orthogonal experiment was carried out to select the optimal formula according to the floating time and drug release.The quality of the floating sustained-release capsule of DDE was evaluated,and study on pharmacokinetics was carried out in animal experiments.METHODS The formulation of the floating sustained-release capsule of DDE was selected by design using PEG6000 as the carrier of solid dispersion,HPMC as the matrix.According to the dissolution rate and floating capacity,the orthogonal design method was used to optimized of floating sustained-release capsule of DDE,and the differential scanning calorimeter ( DSC ) was used to identify the state of the drug existence.The preliminary evaluation of relative bioavailability in the animal models was carried out by single-dose crossover design,the plasma concentration of DDE was determined by HPLC and the pharmacokinetical parameters were calculated by 3P97 Program.RESULTS The release profile of floating sustained-release capsule of DDE in vitro fitted into first-order kinetics . The floating sustained-release capsule of DDE could maintain floating in vitro at least 6 hours.Results of the stability experiments indicated that the capsule could be kept stable at (40℃),RH(75%)for 6 months.An HPLE method for determination of DDE in rabbits plasma was established.The Tmax of DDE floating sustained-release capsule and the common dripping pills were 4.06h and 2.14h,the Cmax were 0.77 and 0.57μg·ml^-1,the bioavailability of floating sustained-release capsule was 110.3%.Significant deviation in bioavailability was observes between common pills and DDE floating sustained-release capsule.