消炎痛缓释胶囊的生物利用度研究

消炎痛普通制剂口服吸收迅速,可出现不必要的高血药浓度,导致不良反应。为此我们对三种消炎痛缓释胶囊(A,B,C)和一种常用片剂(D)作了体外溶出试验和体内生物利用度比较。胶囊制剂由丙烯酸类树脂材料E_(30)D包衣的药物小丸制成,其体外溶出行为显示缓慢释放图象。在8名成年男性交叉实验中,不同胶囊制剂和普通片剂之间的Tmax,Cmax和AUC_(0～124)经方差分析无统计学差异,但是在给药后4至12小时的血清浓度—时间曲线,均比普通片剂高而平滑。在第12小时,三种胶囊产生的血清浓度显著高于普通片剂(P<0.1)。根据体外溶出行为和体内生物利用度发现T_(50)或Tmax和包衣厚度呈良好线性关系。

STUDIES ON BIOAVAILABILITY OF SUSTAINED RELEASE INDOMETHACIN CAPSULES

In order to avoid high initial peak of the commercially available indomethacin formulation and increase the interval between dosages, comparison of three sustained release indomethacin capsules on pellet coated with Eudragit-E_((?)0)D and a commercially available tablet was carried out by testing in vitro the dissolution behaviour and in vivo bioavailability. Dissolution studies on three batches of pellet capsules with varying drug to coat material ratios (mg/cm~2) exhibited a sustained release pattern. In vivo serum level for 8 adult male subjects of randomized crossover design showed no statistical difference in bioavailability between different capsule formulations and a tablet formulation available on the market. However, these three capsule formulations demonstrated a higher and smoother serum concentrationtime curves than that of the tablet formulation from 4 to 12 h following a single dose(50mg). The serum level of three capsule formulations was significantly higher than that of the tablet formulation (P<0.1) at the 12th h respectively. In vitro dissolution behaviour and in vivo bioavailability, the linear relationships were found between T_(50) or T_(m(?)x) and drug to coat material ratios.