Szalai Boglárka, Jójárt-Laczkovich Orsolya, Kovács Anita, Berkó Szilvia, Balogh György Tibor, Katona Gábor, Budai-Szűcs Mária
Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös Str. 6, H-6720 Szeged, Hungary.
Department of Pharmacodynamics and Biopharmacy, Faculty of Pharmacy, University of Szeged, Eötvös Str. 6, H-6720 Szeged, Hungary.
Gels. 2022 Sep 2;8(9):561. doi: 10.3390/gels8090561.
Poor bioavailability of eye drops is a well-known issue, which can be improved by increasing the residence time on the eye surface and the penetration of the active pharmaceutical ingredient (API). This study aims to formulate in situ gelling mucoadhesive ophthalmic preparations. To increase the residence time, the formulations were based on a thermosensitive polymer (Poloxamer 407 (P407)) and were combined with two types of mucoadhesive polymers. Dexamethasone (DXM) was solubilized by complexation with cyclodextrins (CD). The effect of the composition on the gel structure, mucoadhesion, dissolution, and permeability was investigated with 3 full factorial design. These parameters of the gels were measured by rheological studies, tensile test, dialysis membrane diffusion, and in vitro permeability assay. The dissolution and permeability of the gels were also compared with DXM suspension and CD-DXM solution. The gelation is strongly determined by P407; however, the mucoadhesive polymers also influenced it. Mucoadhesion increased with the polymer concentration. The first phase of drug release was similar to that of the CD-DXM solution, then it became prolonged. The permeability of DXM was significantly improved. The factorial design helped to identify the most important factors, thereby facilitating the formulation of a suitable carrier for the CD-DXM complex.
滴眼液生物利用度低是一个众所周知的问题，可通过增加其在眼表的停留时间以及活性药物成分（API）的渗透来改善。本研究旨在制备原位凝胶化的黏膜黏附性眼用制剂。为增加停留时间，制剂基于热敏聚合物泊洛沙姆407（P407），并与两种黏膜黏附性聚合物组合。地塞米松（DXM）通过与环糊精（CD）络合而增溶。采用三因素全因子设计研究了组合物对凝胶结构、黏膜黏附性、溶解性和渗透性的影响。通过流变学研究、拉伸试验、透析膜扩散和体外渗透性试验测定了凝胶的这些参数。还将凝胶的溶解性和渗透性与DXM混悬液和CD-DXM溶液进行了比较。凝胶化强烈地由P407决定；然而，黏膜黏附性聚合物也对其有影响。黏膜黏附性随聚合物浓度增加而增强。药物释放的第一阶段与CD-DXM溶液相似，随后延长。DXM的渗透性显著提高。全因子设计有助于确定最重要的因素，从而便于为CD-DXM复合物配制合适的载体。
