Ghazal Heba S, Dyas A Mark, Ford James L, Hutcheon Gillian A
School of Pharmacy and Chemistry, Liverpool John Moores University, Liverpool, UK.
Int J Pharm. 2009 Jan 21;366(1-2):117-23. doi: 10.1016/j.ijpharm.2008.09.003. Epub 2008 Sep 11.
Drugs in the gastrointestinal tract are exposed to a medium of partially digested food, comprising mixtures of fat, protein and carbohydrate. The dissolution behaviour of itraconazole was evaluated in bio-relevant media which were developed to take this into account. Media containing milk with different fat contents, protein (albumin, casein, gluten and gelatin), carbohydrates (glucose, lactose and starch) and amino acids (lysine, glycine, alanine and aspartic acid) to mimic a digested meal and bile components (sodium taurocholate and lecithin) to represent a key endogenous digestive material were investigated. The effect of medium composition on the intrinsic dissolution rate of itraconazole was evaluated as this drug has extremely poor solubility and its bioavailability is affected by food. Dissolution tests were carried out in simple compendial media based on dilute solutions of hydrochloric acid or neutral solutions of phosphate buffer and in more complex media containing the dietary components. The data obtained showed that most of the dietary components enhanced the solubility compared to simulated gastric fluid (SGF) but to differing extents. The greatest increase in dissolution was observed with the addition of milk and albumin although an increase was also seen with other proteins, amino acids and simulated gastrointestinal fluids.
胃肠道中的药物会接触到一种由部分消化的食物组成的介质，该介质包含脂肪、蛋白质和碳水化合物的混合物。考虑到这一点，在生物相关介质中评估了伊曲康唑的溶解行为。研究了含有不同脂肪含量的牛奶、蛋白质（白蛋白、酪蛋白、麸质和明胶）、碳水化合物（葡萄糖、乳糖和淀粉）和氨基酸（赖氨酸、甘氨酸、丙氨酸和天冬氨酸）以模拟消化后的膳食的介质，以及含有胆汁成分（牛磺胆酸钠和卵磷脂）以代表关键内源性消化物质的介质。由于该药物的溶解度极差且其生物利用度受食物影响，因此评估了介质组成对伊曲康唑固有溶解速率的影响。在基于盐酸稀溶液的简单药典介质或磷酸盐缓冲液的中性溶液以及含有膳食成分的更复杂介质中进行了溶解试验。获得的数据表明，与模拟胃液（SGF）相比，大多数膳食成分提高了溶解度，但程度不同。添加牛奶和白蛋白后观察到溶解增加最大，尽管其他蛋白质、氨基酸和模拟胃肠液也有增加。
