Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University (Parkville Campus), Melbourne, Victoria, Australia.
Int J Pharm. 2013 Jan 30;441(1-2):323-33. doi: 10.1016/j.ijpharm.2012.11.024. Epub 2012 Nov 23.
In vitro digestion testing is of practical importance to predict the fate of drugs administered in lipid-based delivery systems. Calcium ions are often added to digestion media to increase the extent of digestion of long-chain triglycerides (LCTs), but the effects they have on phase behaviour of the products of digestion, and consequent drug solubilization, are not well understood. This study investigates the effect of calcium and bile salt concentrations on the rate and extent of in vitro digestion of soybean oil, as well as the solubilizing capacity of the digestion products for two poorly water-soluble drugs, fenofibrate and danazol. In the presence of higher concentrations of calcium ions, the solubilization capacities of the digests were reduced for both drugs. This effect is attributed to the formation of insoluble calcium soaps, visible as precipitates during the digestions. This reduces the availability of liberated fatty acids to form mixed micelles and vesicles, thereby reducing drug solubilization. The use of high calcium concentrations does indeed force in vitro digestion of LCTs but may overestimate the extent of drug precipitation that occurs within the intestinal lumen.
体外消化试验对于预测脂质给药系统中药物的命运具有实际意义。为了增加长链甘油三酯（LCT）消化的程度，通常会向消化介质中添加钙离子，但人们对其对消化产物的相行为以及随之而来的药物增溶作用的影响还了解甚少。本研究考察了钙离子和胆汁盐浓度对大豆油体外消化速率和程度的影响，以及消化产物对两种疏水性差的药物非诺贝特和丹那唑的增溶能力。在存在较高浓度的钙离子的情况下，两种药物的消化物的增溶能力都降低了。这种效应归因于形成不溶性的钙皂，在消化过程中可见为沉淀物。这减少了游离脂肪酸形成混合胶束和囊泡的可用性，从而降低了药物的增溶作用。使用高浓度的钙离子确实可以强制进行 LCT 的体外消化，但可能会高估肠腔中发生的药物沉淀的程度。
