Maleate Rosiglitazone Floating Sustained Release Tablet Of Experimental Research

EXPEREMENTAL STUDIES OF ROSIGLITAZONE MALEATE INTRAGASTRIC FLOATING SUSTAINED RELEASE TABLET FENG HAO (Pharmaceutics) CHEN DAWEI WANG ZHIM]7N ABSTRACT Rosiglitazone maleate was an oral anti-diabetic agent, belonged to new thiazolidinediones(TZD), which reduces insulin resistance, an underlying defect of type 2 diabetes. It showed a very good market perspective since Avandia was approved by Food and Drug Administration (FDA) in May , 1999. The new dosage forms of rosiglitazone maleate have not been reported. A new intragastric floating sustained release tablet was designed in this thesis, which aimed to delay the gastrointestinal residence time, decease administrated times within day, and have a bio-equivalent to the fast-released tablet. Gastric floating sustained-released tablet was a novel oral dosage form, designed by the principle of hydrodynamically balanced system. On basis of pre-experiments and pharmaceutical pre-formulation studies, the amount and types of expicents, prepared methods and drug release in vitro of the prescription were determined by buoyant and drug releasing conditions as screening index with orthogonal design test and single-factor test methods. Drug releasing process of testing tablet in media was accorded to Higuchi equation, and the releasing mechanism was anomalous diffusion. Stability studies indicated that the preparation should be stored in the dry and light- prevented environment. To observe the dynamic changes in gastric retention, Rg-M sustained- release tablet and control tablet (Avandia) were radio-labeled with 99mTc, their behavior in stomach were detected by i -ray camera techniques. The testing tablet was remained in the stomach for more than 3h without disintegrating. Pharmacokinetic parameters of control and sustained-releasing tablets were studied. The pharmacokinetic parameters of control group (Avandia) in healthy volunteers were similar to that of published. It was suggested that these 3 two preparations were bioequivalent in single oral administration. The cumulative releasing of Rg-M in vitro was related to the absorption fraction in vzvo. Our thesis will be benefit for the development of sustained release dosage forms of rosiglitazone maleat.