Development of sustained-release tablets containing sodium valproate: in vitro and in vivo correlation.
We have developed a 200 mg and 400 mg sustained-release sodium valproate tablet that allows effective blood concentration of the active drug with once-a-day dosing. The controlled dissolution or sustained release of the drug was attained by a membrane-controlled system. A single-coating system did not adequately control the dissolution rate, and therefore double-coated tablets were prepared and a human pharmacokinetic study was conducted. With the 200 mg VPA-Na tablets, the nonfasting C(max) was only 20% higher than the fasting C(max). An in vitro dissolution test was conducted to predict the effects of food on drug dissolution after administration of this tablet. A relatively good correlation was observed between the absorption profiles and the dissolution profiles of the drug.
Pharmaceutical Research Laboratories, Nikken Chemicals Co., Ltd, 1-346, Kitabukuro-cho, Omiya-ku, Saitama-shi, Saitama 330-0835, Japan. y-fujisaki@nikken-chemicals.co.jp
Yuki
Y
Fujisaki
Tadashi
T
Tsukune
Motomu
M
Funyû
Mutsuo
M
Okumura
Tadashi
T
Ukigaya
Kenji
K
Sugibayashi
D000180:Acrylic Resins / Q000737:chemistry; D000927:Anticonvulsants / Q000008:administration & dosage* / Q000493:pharmacokinetics*; D019540:Area Under Curve; D002482:Cellulose / Q000031:analogs & derivatives / Q000737:chemistry; D018592:Cross-Over Studies; D003692:Delayed-Action Preparations; D004305:Dose-Response Relationship, Drug; D005215:Fasting; D006801:Humans; D065347:Hypromellose Derivatives; D008747:Methylcellulose / Q000031:analogs & derivatives / Q000737:chemistry; D019518:Postprandial Period; D012995:Solubility; D013607:Tablets; D014635:Valproic Acid / Q000008:administration & dosage* / Q000493:pharmacokinetics*
D000180:Acrylic Resins; D000927:Anticonvulsants; D003692:Delayed-Action Preparations; D013607:Tablets; D065347:Hypromellose Derivatives; D014635:Valproic Acid; C013517:ethyl cellulose; D002482:Cellulose; D008747:Methylcellulose