Mechanism On Gastric Retention Dosage Forms And Study On Twolayer Floating Sustained Release Tablet Of Cisapride For Gastric Retention

Sustained release floating dosage forms for gastric retention are designed according to the principle of Hydrodynamically Balanced System. Unlike the conventional sustained release dosage forms, this kind of special sustained release dosage will float on the surface of gastric content when taken orally and its gastric retention is rarely influenced. Under the guidance of the law of Archimede and the discovery that buoyancy duration is the key factor determining the gastric retention of the floating dosage, the experiment was carried by studying the floatage and integrity梩he preconditions for floating dosage for gastric retention from following four aspects, that is water uptake kinetics, swelling kinetics, eroding kinetics and floating kinetics. For the floating tablet made of hydrophilic macromolecular materials, buoyancy generation and duration is controlled by the water uptake and swelling of the floating tablet. Lowing the manufacturing pressure can make tablets with low density and greater initial buoyancy. However, for the tablet of lower density, the accelerated water uptake will then increase the tablet density and decrease the buoyancy duration. That is why some hydrophobic ingredients should be added in order to made floating tablet with ideal floating duration other than decreasing the tableting pressure alone. According to the eroding kinetics, the floating tablet made of HPMC with greater viscosity as Kl00 MCR and K15 MCR is better than that made of HPMC E 15 LV. The erosion of the tablet made of HPMC E 15 LV followed the first order kinetics. 20 % of the tablet eroded with 4 hours which is 22 times that of the tablet made of HPMC K 100 MCR. The fast erosion of the tablet made of HPMC E 15 LV led to quick buoyancy decrease. The quick swelling of floating tablet made of CMC-Na led to quicker water uptake. Moreover, its quick erosion at a speed of 30% within 4 hours of its original weight led to buoyancy decrease. Evaluation by similarity showed that the type of materials other than pressure determine the tablet erosion. The buoyancy of tablet made of water insoluble Eudragit RS P0 generally comes from its density. Because of the influence from tablet erosion on the buoyancy, single or two-layer tablet can be made if the drug dissolves well in gastric content. For drugs that dissolute by means of tablet erosion, two-layer tablet should be made. One layer is for buoyancy and the other for drug release. Otherwise, tablet erosion will lead to simultaneous buoyancy decrease. A two條ayer floating tablet for gastric retention was made using cisapride as a model 3 drug. In order to improve the solubility of the model drug, solid dispersion was made using HPMC E 15 LV as carrier at a ratio of 1:4 ( drug:carrier). The solubility of cisapride was increased by3.39, 2.32 and 2.18 times in water SGF and SW separately. As to the in vitro buoyancy test, the tablet went up to medium surface in less than 10 mm. A floating ability as great as 100 Dyne was maintained for more than 6 h. A zero order in vitro drug release as long as 8-12 h was achieved when simulated gastric fluid was used as dissolution medium. The in vitro dissolution in simulated gastric fluid (SGF) is faster than in simulated intestinal fluid (SiT) because the drug has a greater solubility in SGF than in SIT. Tablet erosion and drug dissolution does not go simultaneously if SW is used. Counter extraction was used for processing the bl...