索法酮胃内漂浮型缓释片的研制

Preparation of Sofalcone Intragastric Floating Sustained-release Tablets

以索法酮固体分散体为原料。羟丙甲纤维素(HPMC)为骨架材料,十八醇为助漂剂,碳酸氢钠为泡腾剂,采用粉末直接压片法制备索法酮胃内漂浮型缓释片。以起漂时间和累积释放率为指标,采用正交设计优化处方中HPMC、碳酸氢钠和十八醇的用量。结果表明,十八醇用量的影响最显著。所得优化制品在0.1 mol/L盐酸中的起漂时间短,持漂时间大于12 h,且具有显著的缓释性能。兔体内药动学研究表明,本品c_(max)为(0.6±0.5)μg/ml,t_(max)为(5.3±1.0)h,AUC_(0→∞)为(4.9士0.7)μg·h·ml^(-1)。体外累积释放率与体内吸收分数的相关系数为0.995 49,提示体内外相关性良好(P<0.001)。

The intragastric floating sustained-release tablets were prepared by direct compression with the sofalcone solid dispersion as the raw material, hydroxypropyl methylcellulose （HPMC） as matrix material, octadecanol as floating assistant agent and NaHCO3 as effervescent. The amounts of HPMC, NaHCO3 and octadecanol were optimized by orthogonal design with the floating onset time and in vitro release as the indexes. The results showed that the effect of octadecanol amount was the most remarkable. The optimal tablets with short floating onset time could maintain floating for more than 12 h in 0.1 mol/L hydrochloric acid and had a significant sustained-release profile. The pharmacokinetics in rabbits showed that the c tmax and AUC0-∞ of the product were （0.6±0.5）μg/ml, （5.3±1.0）h and （4.9±0.7）μg·h·ml^-1, respectively. Rate of absorption in vivo was correlated with in vitro release with a correlation coefficient of 0.995 49, which indicated a good correlation between in vitro release and in vivo absorption （P〈0.001）.