关键词: 漂浮, 固体分散体, 尼莫地平, 缓释, 体内转运

Abstract: A novel sustained release gastric floating tablet containing solid dispersion withenhanced bioavailability and prolonged gastrointestinal resident time of the model drug nimodipine,apoorly soluble drug, was manufactured. Solid dispersion of nimodipine was prepared by a solventmelting method using poloxamer 188 as carrier. The floating tablet was made up of nimodipinepoloxamer 188 solid dispersion, hydroxypropylmethylcellulose, magnesium carbonate, hexadecanol,and several other additives. Formulations were optimized using an experimental design. Optimal formulation showed immediate buoyancy after introduction into simulated gastric fluid and maintained asustained floating state for over 10 h. Noninvasive scintigraphy also showed that the dosage formfloated to the surface of the gastric fluid from the bottom of the stomach. Food had an important effect on in vivo transit. Under fed conditions, the floating dosage form seemingly left small intestineabout 5 h after ingestion, and the non-floating tablet was emptied within 3 h. Under fasted conditions,the floating dosage form remained in the stomach and small intestine for only 3 h and the non-floatingtablet disintegrated and left the absorption site within 2 h. Pharmacokinetics in healthy male volunteers indicated that the relative bioavailability of this novel dosage form was about 4 times that of aconventional nimodipine tablet, and the mean resident time was twice that of the conventional tablet.

Key words: Floating, Solid dispersion, Nimodipine, Hydroxypropylmethylcellulose, Bioavailability, Gastrointestinal transit