Preparation Of Tanno Hydrochloride New - Stomach Floating Sustained - Release Pellets

Tamsulosin hydrochloride is a powerful al adrenoceptor antagonists of human prostate, which is used to treat benign prostatic hyperplasia and lower urinary tract symptoms caused by prostatic hypertrophy. Tamsulosin hydrochloride is absorbed quickly and particularly at risk for dizzy adverse events, so the preferred formulation of tamsulosin hydrochloride provides a controlled-release that can be used in clinical. The drug almost has a completely bioavailability but easily affected by food. As a result, the pharmacokinetics parameters of tamsulosin hydrochloride have big difference from empty condition to full condition and its bioavailability of empty condition is thirty percents larger than full condition. The objective of this study is to develop new dosage form-floating stagnation sustained release pellets, contract to common released capsules or pellets, it can float and release slowly. Moreover, this preparation can avoid or diminish food effect, increase safety and have an equivalent bioavailability.A simple and accurate High Performance Liquid Chromatography method was developed for assaying content and drug release of tamsulosin hydrochloride. The stability, solubility and Papp of tamsulosin hydrochloride were investigated. The results of stability showed that tamsulosin hydrochloride was stable. Tamsulosin hydrochloride was sparingly soluble in water and slightly soluble in alcoh,0.1 mol/L hydrochloric acid solution and pH7.2 buffer solution. It has liposolubility and water solubility simultaneously with Papp of 1.24.The single gastrointestinal perfusion technique was adopted to study the mechanisms and pharmacokinetics of drug absorption in vivo. The results showed that tamsulosin hydrochloride could be absorbed at all segments of gastrointestinal tract in rats and its main absorption was stomach, upper and middle of small intestine. So it was a good candidate for the floating stagnation sustained-release system. Drug concentration ranged from 0.4μg/ml to 8.0μg/ml had no significantly effect on the values of Ka and Papp, which indicated that the mechanism of the intestinal absorption of tamsulosin hydrochloride was passive diffusion. Different pH values had no significantly effect on the values of Ka and Papp. Increasing perfusion flow rate produced increasing values of Ka and Papp. Tamsulosin hydrochloride floating stagnation sustained release pellets were prepared by means of power accumulation with the centrifugal granulation technology. Through experiment, it was discovered that the yield and buoyancy of the objective pellets was low, the angles of repose was bad. The results suggested that the centrifugal granulation technology for tamsulosin hydrochloride was not adoptable.Tamsulosin hydrochloride floating stagnation sustained release pellets were prepared by several methods and the results showed that the solvent diffusion and evaporation method was most suitable. The preparation and technology of pellets were optimized with orthogonal experiment. We also studied the stability and release profile model of sustained-release pellets. As a result, the drug release profile followed Higuchi model in vitro. The pellets were stable under high temperature, high humidity and intensive light tests.y-Scintigraphy was used to study the stomach retention of tamsulosin hydrochloride floating sustained release pellets marked by99mTc. As a result, floating pellets prolonged gastrictetetion time of tamsulosin hydrochloride compared to non-floating preparation. Tamsulosin hydrochloride floating sustained release pellets prepared by the solvent diffusion and evaporation method was feasible and significant.