Jantratid Ekarat, De Maio Vincenzo, Ronda Emanuela, Mattavelli Valentina, Vertzoni Maria, Dressman Jennifer B
Institute of Pharmaceutical Technology, Johann Wolfgang Goethe University, Max-von-Laue-Str. 9, 60438 Frankfurt am Main, Germany.
Eur J Pharm Sci. 2009 Jun 28;37(3-4):434-41. doi: 10.1016/j.ejps.2009.03.015. Epub 2009 Apr 5.
In vitro biorelevant dissolution tests enabling the prediction of in vivo performance of an oral modified-release (MR) dosage form were developed in this study. In vitro dissolution of MR diclofenac sodium pellets containing 100mg active ingredient was evaluated under simulated pre- and postprandial conditions using USP Apparatus 3 (reciprocating cylinder, Bio-Dis) and 4 (flow-through cell) and results compared with compendial methods using USP Apparatus 1 (basket) and 2 (paddle). In vivo, the effects of food on the absorption of diclofenac sodium from the pellet dosage form were investigated by administering the product to 16 healthy volunteers pre- and postprandially in a crossover-design study. The in vitro results were compared with the in vivo data by means of Level A in vitro-in vivo correlation (IVIVC) and Weibull distribution analysis. The compendial dissolution tests were not able to predict food effects. The biorelevant dissolution tests predicted correctly that the release (and hence absorption) of diclofenac sodium would be slower in the fed state than in the fasted state. No significant differences in extent of absorption due to changes in extent of release were predicted or observed. The results demonstrate good correlations between in vitro drug release and in vivo drug absorption in both pre- and postprandial states using the biorelevant dissolution test methods.
本研究开发了体外生物相关性溶出试验，以预测口服缓释（MR）剂型的体内性能。使用美国药典装置3（往复圆筒，Bio-Dis）和装置4（流通池），在模拟的餐前和餐后条件下，对含有100mg活性成分的双氯芬酸钠MR微丸的体外溶出度进行了评估，并将结果与使用美国药典装置1（篮法）和装置2（桨法）的药典方法进行了比较。在体内，通过在交叉设计研究中对16名健康志愿者在餐前和餐后给予该产品，研究了食物对双氯芬酸钠从微丸剂型中吸收的影响。通过A级体外-体内相关性（IVIVC）和威布尔分布分析，将体外结果与体内数据进行了比较。药典溶出试验无法预测食物的影响。生物相关性溶出试验正确预测，双氯芬酸钠在进食状态下的释放（以及因此的吸收）将比禁食状态下更慢。未预测到或观察到由于释放程度变化导致的吸收程度有显著差异。结果表明，使用生物相关性溶出试验方法，在餐前和餐后状态下，体外药物释放与体内药物吸收之间均具有良好的相关性。
