Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland; Oculis ehf, Alfheimar 74, 6th Floor, 104 Reykjavik, Iceland.
Faculty of Pharmaceutical Sciences, University of Iceland, Hofsvallagata 53, 107 Reykjavik, Iceland.
J Pharm Sci. 2022 Sep;111(9):2571-2580. doi: 10.1016/j.xphs.2022.04.015. Epub 2022 Apr 27.
Cyclodextrins are hydrophilic oligosaccharides that can increase aqueous solubility of lipophilic drugs through formation of water-soluble drug/cyclodextrin complexes. Although the complexes are hydrophilic, and as such do not permeate biological membranes, the complexes are known to enhance drug permeation through lipophilic membranes and improve drug bioavailability after, for example, oral administration. However, it is not clear how cyclodextrins enhance the permeation. An artificial biomembrane (PermeaPad®) was used to study the effect of donor medium composition on drug permeation. It was observed that in aqueous solutions the hydrophilic cyclodextrins behave not like disperse systems but rather like organic cosolvents such as ethanol, increasing the solubility without having significant effect on the molecular mobility and ability of lipophilic drug molecules to partition into the lipophilic membrane. Also, that partition of dissolved drug molecules from the aqueous exterior into the membrane is at its maximum when their thermodynamic activity is at its maximum. In other words, that drug flux from aqueous cyclodextrin solutions through lipophilic membranes depends on both the concentration and the thermodynamic activity of dissolved drug. Maximum flux is obtained when both the drug concentration and thermodynamic activity of the dissolved drug molecules are at their maximum value.
环糊精是亲水性的低聚糖，可通过形成水溶性药物/环糊精复合物来增加亲脂性药物的水溶解度。尽管这些复合物是亲水性的，因此不会渗透生物膜，但已知它们能够增强亲脂性膜中的药物渗透，并提高例如口服后的药物生物利用度。然而，目前尚不清楚环糊精如何增强渗透。人工生物膜（PermeaPad®）被用于研究供体介质组成对药物渗透的影响。结果表明，在水溶液中，亲水性环糊精的行为不像分散体系，而更像乙醇等有机共溶剂，增加了溶解度，而对脂溶性药物分子的分子迁移率和进入脂溶性膜的能力没有显著影响。此外，当脂溶性药物分子从水相外侧进入膜的热力学活度达到最大时，溶解药物分子的分配达到最大。换句话说，亲脂性膜中从水合环糊精溶液中药物的通量取决于溶解药物的浓度和热力学活度。当溶解药物分子的浓度和热力学活度都达到最大值时，可获得最大通量。
