Institute of Pharmaceutical Technology and Regulatory Affairs, Faculty of Pharmacy, University of Szeged, Eötvös Street 6, Szeged 6720, Hungary.
Institute of Pharmaceutical Sciences, Department of Pharmaceutical Technology and Biopharmacy, University of Graz, Universitaetsplatz 1, Graz 8010, Austria.
Eur J Pharm Sci. 2024 Nov 1;202:106879. doi: 10.1016/j.ejps.2024.106879. Epub 2024 Aug 16.
Nasal systemic drug delivery may provide an easy way to substitute parenteral or oral dosing, however, the excipients have an important role in nasal formulations to increase the permeability of the mucosa and prolong the residence time of the drug. In this work, we aimed to produce meloxicam potassium monohydrate (MXP) containing nasal powders by a nano spray drier with the use of a neutral, an anionic and a cationic β-cyclodextrin as permeation enhancers, and (polyvinyl)alcohol (PVA) as a water soluble polymer. The following examinations were performed in order to study the effect of the applied excipients on the nasal applicability of the formulations: laser scattering, scanning electron microscope measurement, XRPD, DSC and FTIR measurements, adhesivity, in vitro drug release and permeability tests through an artificial membrane and RPMI 2650 cells. Based on our results, spherical particles were prepared with a size of 1.89-2.21 µm in which MXP was present in an amorphous state. Secondary interactions were formed between the excipients and the drug. The charged cyclodextrin-based formulations showed significantly higher adhesive force values regardless of the presence of PVA. The drug release was fast and complete. The passive diffusion of MXP was influenced not only by the charge of the cyclodextrin, but the presence of PVA, too. The permeation of the drug was enhanced in the presence of the anionic cyclodextrin testing it on RPMI 2650 cell model.
鼻腔全身给药可能提供一种替代肠外或口服给药的简便方法，然而，赋形剂在鼻腔制剂中具有重要作用，可增加黏膜的通透性并延长药物的停留时间。在这项工作中，我们旨在通过纳米喷雾干燥器生产含有美洛昔康钾一水合物（MXP）的鼻腔粉末，使用中性、阴离子和阳离子β-环糊精作为渗透增强剂，（聚乙烯）醇（PVA）作为水溶性聚合物。为了研究所应用的赋形剂对制剂鼻腔适用性的影响，进行了以下检查：激光散射、扫描电子显微镜测量、XRPD、DSC 和 FTIR 测量、粘附性、体外药物释放和通过人工膜和 RPMI 2650 细胞的渗透性测试。基于我们的结果，制备了尺寸为 1.89-2.21 µm 的球形颗粒，其中 MXP 以无定形状态存在。赋形剂和药物之间形成了次级相互作用。带电荷的环糊精制剂表现出显著更高的粘附力值，无论是否存在 PVA。药物释放快速且完全。MXP 的被动扩散不仅受环糊精电荷的影响，还受 PVA 的存在影响。在存在阴离子环糊精的情况下，药物的渗透得到增强，并在 RPMI 2650 细胞模型上进行了测试。
