Formulation and Pharmacokinetic Evaluation of Sustained Release Preparation Containing Clebopride Malate

말산클레보프리드 서방성 제제의 제조 및 약물동태학적 평가

Clebopride malate(Cm) is a new benzamide drug which has a potent central antidopaminergic activity possessing antiemetic and anxiolytic properties. A purpose of this study was to assess the feasibility of formulating sustained release preparation by dispersing a drug in hydrophilic polymeric matrices and double layered tablets(DLT), using HPMC, carbopol, PEO, PVP/VA and other polymers as a rate controlling barrier. The matrix and DLT showed optimum dissolution pattern up to 8 hours and the contents of polymer were optimized at 30% level in this preparation. After an oral administration in beagle dog, Cm concentration was determined by use of GC-ECD and pharmacokinetic parameters were calculated by Vallner's method. The AUC of DLT showed similar results and the duration of action was increased 55% compared to that of regular release dosage form. The calculated absorption rate effectiveness(ARE) and controlled release effectiveness(CRE) for DLT increased 50% compared to that of matrix, the overall effectiveness(E) of this product appears to be about 70%. in vivo effectiveness test, DLT showed significant differences from control on antiemetic action of Cm. In consequence, it was possible to conclude that double layered tablet might be a good candidate for the sustained release dosage forms.