Biomedical Science, Faculty of Health and Society, Malmö University, SE-205 06 Malmö, Sweden; Biofilms - Research Center for Biointerfaces (BRCB), Malmö University, SE-205 06 Malmö, Sweden.
Nanologica AB, SE-151 36 Södertälje, Sweden; Chemistry Department, KTH, Royal Institute of Technology, 100 44 Stockholm, Sweden.
Eur J Pharm Sci. 2021 Nov 1;166:105983. doi: 10.1016/j.ejps.2021.105983. Epub 2021 Aug 27.
Oral transmucosal drug delivery is a non-invasive administration route for rapid therapeutic onset and greater bioavailability avoiding the first-pass metabolism. Mucoadhesive formulations are advantageous as they may retain the drug at the administration site. Proper equipment to assess mucoadhesive properties and corresponding drug absorption is fundamental for the development of novel drug delivery systems. Here we developed a new flow-through donor chamber for well-established diffusion cells, and we tested the effects on drug and formulation retention in situ of adding mucoadhesive polymers or mesoporous silica particles to a reference formulation. Mesoporous silica particles are of particular interest as they may be used to encapsulate and retain drug molecules. Compared to other ex-vivo methods described in literature for assessing mucoadhesive performance and transmucosal drug delivery, this new donor chamber provides several advantages: i) it reflects physiological conditions better as a realistic saliva flow can be provided over the administration site, ii) it is versatile since it can be mounted on any kind of vertical diffusion cell allowing simultaneous detection of drug retention at the administration site and drug permeation through the tissue, and iii) it enables optical quantification of formulations residence time aided by image processing. This new flow-through donor diffusion cell set-up proved sensitive to differentiate a reference formulation from one where 20 %(w/w) Carbomer was added (to further improve the mucoadhesive properties), with respect to both drug and formulation residence times. We also found that mesoporous silica particles, investigated as particles only and mixed together with the reference formulation, gave very similar drug and formulation retention to what we observed with the mucoadhesive Carbomer. However, after some time (>30 min) it became obvious that the tablet excipients in the reference formulation promote particle retention on the mucosa. This work provides a new simple and versatile biorelevant test for the evaluation of oral mucoadhesive formulations and paves the way for further studies on mesoporous silica particles as valuable excipients for enhancing oral mucoadhesion.
口腔黏膜给药是一种非侵入性给药途径，可快速起效，生物利用度更高，避免首过代谢。黏膜黏附制剂具有优势，因为它们可以将药物保留在给药部位。适当的设备来评估黏膜黏附特性和相应的药物吸收对于新型药物输送系统的开发至关重要。在这里，我们为现有的扩散池开发了一种新的流通式供体室，并测试了向参考制剂中添加黏膜黏附聚合物或介孔硅颗粒对药物和制剂原位保留的影响。介孔硅颗粒特别有趣，因为它们可以用于包封和保留药物分子。与文献中描述的其他用于评估黏膜黏附性能和经黏膜药物传递的离体方法相比，这种新的供体室具有以下几个优点：i）它可以更好地反映生理条件，因为可以在给药部位提供真实的唾液流动，ii）它具有多功能性，因为它可以安装在任何类型的垂直扩散池上，允许同时检测药物在给药部位的保留和药物通过组织的渗透，iii）它可以通过图像处理实现制剂停留时间的光学定量。这种新的流通式供体扩散池装置对区分参考制剂和添加 20%（w/w）卡波姆（以进一步改善黏膜黏附性能）的制剂非常敏感，无论是药物还是制剂的停留时间。我们还发现，作为颗粒单独研究并与参考制剂混合的介孔硅颗粒，与我们观察到的黏膜黏附卡波姆相比，对药物和制剂的保留非常相似。然而，一段时间后（>30 分钟），很明显参考制剂中的片剂赋形剂促进了颗粒在黏膜上的保留。这项工作为评价口腔黏膜黏附制剂提供了一种新的简单而多功能的生物相关测试方法，并为介孔硅颗粒作为增强口腔黏膜黏附的有价值赋形剂的进一步研究铺平了道路。
