Existing in vitro dissolution or permeation models to predict food effect are mainly based on Pharmacopeias' compendial media, which specify such variables as pH, bile salts, lipolytic enzymes, and phospholipids content. However, the viscosity of food in the gastrointestinal (GI) tract is not taken into account, although it can affect both the dissolution of the oral solid dosage form and absorption of the released drug. Here, a new in vitro dissolution absorption system (IDAS2) is utilized, which comprises a dissolution apparatus USP2 (DISTEK) equipped with specially constructed permeability chambers containing Caco-2 monolayers, thereby allowing dissolution and transepithelial absorption to be ascertained simultaneously. The IDAS2 was used to evaluate the effect of medium viscosity on both the dissolution of oral solid dosage forms and absorption of released drugs. Such information, which is not ordinarily determined in dissolution and permeation studies, will be helpful to the formulators developing robust oral dosage forms. Commercially available solid dosage forms of ten model drugs from across all BCS classifications were used in this evaluation: metoprolol, minoxidil, and propranolol from BCS class 1; carbamazepine, ketoprofen, and simvastatin from BCS class 2; atenolol and ranitidine from BCS class 3; and acetazolamide and saquinavir from BCS class 4. The study revealed the applicability of IDAS2 as a tool for in vitro screening of dissolution and absorption of intact oral solid products to predict food viscosity effect. The most profound viscosity effect on dissolution and absorption was observed of solid dosage forms for the BCS class 2 compounds carbamazepine and simvastatin. A higher medium viscosity significantly slowed down the dissolution rate of tested BSC class 4 compounds acetazolamide and saquinavir, without significant effect on their absorption. The solid dosage forms least affected by the viscosity of the medium tested were the BCS class 1 compounds minoxidil and propranolol.

中文翻译：

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体外溶出吸收系统（IDAS2）：用于预测食品粘度对口服固体剂型对药物溶出和吸收的影响。

现有的预测食物效果的体外溶出或渗透模型主要基于药典的药典培养基，该药典规定了诸如pH，胆汁盐，脂解酶和磷脂含量等变量。然而，尽管它会影响口服固体剂型的溶解和释放药物的吸收，但并未考虑食物在胃肠道中的粘度。在这里，使用了一种新的体外溶出吸收系统（IDAS2），该系统包括一个溶出设备USP2（DISTEK），该设备配备有专门构造的包含Caco-2单层的渗透腔，从而可以同时确定溶出和上皮吸收。IDAS2用于评估中等粘度对口服固体剂型溶解和释放药物吸收的影响。此类信息通常在溶出度和渗透性研究中无法确定，将有助于配方设计师开发出坚固的口服剂型。评估中使用了来自所有BCS分类的十种模型药物的市售固体剂型：来自BCS 1类的美托洛尔，米诺地尔和普萘洛尔；BCS 2类的卡马西平，酮洛芬和辛伐他汀；来自BCS 3类的阿替洛尔和雷尼替丁; 以及来自BCS 4类的乙酰唑胺和沙奎那韦。该研究表明IDAS2作为体外筛选完整口服固体产品的溶解和吸收以预测食品粘度影响的工具的适用性。观察到BCS 2类化合物卡马西平和辛伐他汀的固体剂型对溶解和吸收的影响最深远。较高的中等粘度会显着减慢测试的BSC 4类化合物乙酰唑胺和沙奎那韦的溶解速度，而对其吸收没有显着影响。受测试介质粘度影响最小的固体剂型是BCS 1类化合物米诺地尔和普萘洛尔。