盐酸维拉帕米渗透泵片溶出度与人体生物利用度研究

STUDY ON DISSOLUTION TEST IN VITRO AND BIOAVAILABILITY OF ORAL OSMOTIC PUMP OF VERAPAMIL HYDROCHLORIDE

摘要: 溶出度按Weibull's分布处理得T_d=5.76 h,T₅₀=3.9 h,零级溶出速度常数K_t=9.9450,平均体外溶解时间MDT=5.391 h。测定8名健康受试者,单剂量口服,得C_max=76.2±16.7 ng/ml,T_amx=8.0 h,t_1/2=9.75 h,MRT=19.41 h,MAT=5.34 h,与Knoll公司SR片相比,F_rel=101.71%;与市售普通片相比,F_rel=96.16%。多剂量口服,得C_max=121.47±34.5 ng/ml,T_max=7.14 h。按Loo-Riegelman方程处理表明体内外显著相关。理论值与实测值基本相符。

Abstract: This paper deals with the evaluation of osmotic pump of verapamil hydrochloridetablet(C) by measuring in vitro/in vivo test. The results showed that the dissolution behaviors were of zero-order kinetic and release constant in vitro(Kr) of C was 9.9450. The plasma levels of Ver·HCl in eight volunteers following single and multiple oral doses of these dosage forms were determined using HPLC method. The pharmacokinetic parameters were fitted by nonlinear least square method with a computer on the basis of two-compartment model. The pharmacokinetic parameters of C_max, T_max, t_1/2, K_A, K₁₀ and K₂₁ were calculated. The bioavailability of tablet C relative to B and A was 101.7%, 96. 16% respectively. A significant correlation was found between in vitro dissolution and in vivo absorption.