国内外阿那曲唑片溶出曲线相似性评价及采用GastroPlus^(TM)建立体内外相关性模型的研究

Evaluation for the Dissolution Curve Similarity of Domestic and Overseas Anastrozole Tablets and Study on the Establishment in Vivo-in Vitro Correlation Model by GastroPlus^(TM)

目的建立阿那曲唑片新溶出度检查方法,研究阿那曲唑的溶出行为,评价国内3家片剂产品与原研片溶出曲线的相似性;并建立体内外相关性模型,预测口服阿那曲唑片的药动学参数,评价其生物等效性。方法新溶出度检查方法:桨法,50 r·min^(-1),溶出介质为水900 mL,30 min取样,HPLC测定,限度为标示量的80%。通过Gastro PlusTM软件,结合体外溶出实验结果,建立体内外相关性模型。结果新建立的溶出度检查方法在0.22~1.10μg·mL^(-1)内与峰面积呈良好的线性关系,平均回收率为99.3%(RSD=0.8%,n=9)。国内3家制药公司产品与原研样品在4种溶出介质中的溶出曲线均相似。溶出曲线与软件模拟的体内行为非常相似,吻合度较高。结论采用浆法,转速为50 r·min^(-1),能有效的控制本品的质量。通过体内外相关性的分析,可见建立的体外溶出方法能较好地体现阿那曲唑片在体内的溶出行为。

OBJECTIVE To develop a new dissolution method of anastrozole tables, study the dissolution behavior, and evaluate the dissolution behavior of consistency between Chinese three companies and the original tablet. And to establish in vivo-in vitro correlation model, predict of anastrozole tablets oral pharmacokinetic parameters and evaluate its bioequivalence. METHODS Apparatus 2 was used with 50 r·min^（-1）, the dissolutive medium was water 900 m L, the dissolutive solution was taken and analyzed by HPLC when 30 min and the limitation was 80% in the new method for dissolution test. Combined with the results of in vitro dissolution curve, establish in vivo correlation model by Gastro PlusTM. RESULTS The new method of dissolution test had good linear relationship with the peak area in the range of 0.22-1.10 μg·m L-1, and the average recovery rate was 99.3%（RSD=0.8%, n=9）, which was highly accurate and could be used for the determination of dissolution curve. The three domestic pharmaceutical company products were all in line with the original research sample in the dissolution curve similarities of the four media. The dissolution curve was similar to the in vivo behavior of the software, and the coincidence was high. CONCLUTION The quality of this product can be effectively controlled by Apparatus 2 used with 50 r·min^（-1）. Through the analysis of in vivo-in vitro correlation, the dissolution behavior in vitro can better reflect the dissolution behavior in vivo.