Hörter D, Dressman J B
Institut für Pharmazeutische Technologie, J.W. Goethe Universität, Marie-Curie-Strasse 9, 60439 Frankfurt am Main, Germany.
Adv Drug Deliv Rev. 2001 Mar 1;46(1-3):75-87. doi: 10.1016/s0169-409x(00)00130-7.
The rate-limiting step to absorption of drugs from the gastrointestinal (GI) tract is often dissolution from the dosage form. Consideration of the Noyes-Whitney dissolution model shows that drug diffusivity, solubility in the gastrointestinal contents, the surface area of the solid wetted by the lumenal fluids and the GI hydrodynamics all play a role in determining the in vivo dissolution rate. Solubility in the GI contents is determined by aqueous solubility, crystalline form, drug lipophilicity, solubilization by native surfactants and co-ingested foodstuffs, and pK(a) in relation to the GI pH profile. Compounds with aqueous solubilities lower than 100 microg/ml often present dissolution limitations to absorption. The dose:solubility ratio of the drug provides an estimate of the volume of fluids required to dissolve an individual dose, and when this volume exceeds 1 l, dissolution is often problematic. The surface area of a drug available for dissolution depends on the particle size of the solid and its ability to be wetted by lumenal fluids. Other physiological factors that can play a role in dissolution include the viscosity of the lumenal contents, through its effect on the diffusivity, and mixing and flow patterns within the gut. In order to better predict in vivo dissolution of drugs, dissolution tests which more adequately simulate the physiological conditions are needed.
药物从胃肠道吸收的限速步骤通常是从剂型中溶解出来。对诺伊斯 - 惠特尼溶解模型的研究表明，药物扩散系数、在胃肠道内容物中的溶解度、被腔内液体润湿的固体表面积以及胃肠道流体动力学均在决定体内溶解速率方面发挥作用。在胃肠道内容物中的溶解度由水溶性、晶型、药物亲脂性、天然表面活性剂和同时摄入的食物的增溶作用以及与胃肠道pH分布相关的pK(a)决定。水溶性低于100μg/ml的化合物通常对吸收存在溶解限制。药物的剂量：溶解度比可估算溶解单个剂量所需的液体体积，当该体积超过1升时，溶解通常会出现问题。可供溶解的药物表面积取决于固体的粒径及其被腔内液体润湿的能力。其他可在溶解过程中发挥作用的生理因素包括腔内内容物的粘度（通过其对扩散系数的影响）以及肠道内的混合和流动模式。为了更好地预测药物的体内溶解情况，需要能更充分模拟生理条件的溶解试验。
