Department of Pharmacy, Uppsala University, Uppsala, Sweden.
Colloids Surf B Biointerfaces. 2012 Jan 1;89:53-60. doi: 10.1016/j.colsurfb.2011.08.022. Epub 2011 Sep 6.
To fully utilize the extended contact time of gel formulations a novel formulation with drug containing catanionic aggregates offering prolonged drug release and skin penetration were investigated. This study aimed to further explore the drug release process from catanionic vesicles in gels. Catanionic vesicles were formed from alprenolol and sodium dodecyl sulphate. Physical gels composed of catanionic vesicles and a SoftCAT polymer were used as well as covalent Carbopol gels. Drug release was measured in vitro using a modified USP paddle method and the skin penetration was studied using dermatomized pig ear skin mounted in horizontal Ussing chambers. The aggregate structure was visualized with cryo-TEM during the drug release and skin penetration process. The study results show that catanionic vesicles are present in the formulations throughout the drug release process and during the clinically relevant skin application time. Hence, the decreased skin penetration rate stems from the prolonged release of drug substance from the gels. The rheological investigation shows that the gel structure of the physically cross-linked gels is maintained even as the drug substance is released and the gel volume is decreased. These findings indicate that the applicability of formulations like these is a future possibility.
为了充分利用凝胶制剂的延长接触时间，研究了一种含有两性离子聚集体的新型制剂，该制剂具有延长药物释放和皮肤渗透的作用。本研究旨在进一步探索凝胶中两性离子囊泡的药物释放过程。两性离子囊泡由阿普洛尔和十二烷基硫酸钠形成。还使用了由两性离子囊泡和 SoftCAT 聚合物组成的物理凝胶以及共价 Carbopol 凝胶。使用改良的 USP 桨法在体外测量药物释放，使用安装在水平 Ussing 室中的去皮猪耳皮肤研究皮肤渗透。在药物释放和皮肤渗透过程中，使用冷冻 TEM 可视化了聚集结构。研究结果表明，两性离子囊泡在制剂中存在于整个药物释放过程中，以及在临床相关的皮肤应用时间内。因此，皮肤渗透速率的降低源于从凝胶中释放出的药物物质的延长释放。流变学研究表明，即使药物物质释放并且凝胶体积减小，物理交联凝胶的凝胶结构也得以保持。这些发现表明，这些制剂的适用性是未来的一种可能性。
