Armstrong N A, James K C, Pugh W K
J Pharm Pharmacol. 1984 Jun;36(6):361-5. doi: 10.1111/j.2042-7158.1984.tb04399.x.
Analysis of the shells and contents of soft gelatin capsules containing acetomenaphthone, ephedrine, 4-hydroxyenzoic acid or phenobarbitone, dissolved in isopropyl myristate, revealed that the percentage of solute taken up by the shells increased with increasing aqueous solubility of the substrate. Thus no acetomenaphthone, which has a negligible aqueous solubility, was found in the shells, in comparison with 92% of the 4-hydroxybenzoic acid, which has a significant solubility in water. Uptake was not influenced by the solubility in isopropyl myristate. The effect of the oily solvent was studied using blends of 1-octanol and isopropyl myristate in which either 4-hydroxybenzoic acid or phenobarbitone were dissolved. Solute release shows that both release and migration can be predicted from a knowledge of the aqueous solubility of the solute and its partition coefficient between water and the non-polar solvent. Samples of capsules containing 4-hydroxybenzoic acid in isopropyl myristate were withdrawn at various stages of the manufacturing process, and the distributions between shell and contents noted. Most of the transfer took place while the capsules were being dried in rotating basket driers, and at this point 67% of the acid had migrated. This increased to 92% during tray drying, and remained so for at least 6 months after manufacture.
对含有醋甲萘醌、麻黄碱、4-羟基苯甲酸或苯巴比妥并溶解于肉豆蔻酸异丙酯中的软胶囊的外壳及内容物进行分析后发现，外壳摄取溶质的百分比随底物水溶性的增加而增加。因此，由于醋甲萘醌的水溶性可忽略不计，在外壳中未发现其存在，相比之下，在水中具有显著溶解度的4-羟基苯甲酸在外壳中的含量为92%。摄取不受在肉豆蔻酸异丙酯中的溶解度影响。使用溶解有4-羟基苯甲酸或苯巴比妥的1-辛醇与肉豆蔻酸异丙酯的混合物研究了油性溶剂的作用。溶质释放表明，释放和迁移均可根据溶质的水溶性及其在水和非极性溶剂之间的分配系数来预测。在制造过程的各个阶段取出含有肉豆蔻酸异丙酯中4-羟基苯甲酸的胶囊样品，并记录外壳与内容物之间的分布情况。大部分转移发生在胶囊在旋转篮式干燥器中干燥时，此时67%的酸已迁移。在托盘干燥期间，这一比例增加到92%，并且在制造后至少6个月内保持不变。
