Kiel University, Department of Pharmaceutics and Biopharmaceutics, Gutenbergstraße 76, 24118 Kiel, Germany.
Kiel University, Department of Pharmaceutics and Biopharmaceutics, Gutenbergstraße 76, 24118 Kiel, Germany; Priority Research Area Kiel Nano, Surface and Interface Sciences (KiNSIS), Kiel University, Kiel, Germany.
Int J Pharm. 2023 Feb 25;633:122630. doi: 10.1016/j.ijpharm.2023.122630. Epub 2023 Jan 20.
The nasal physiology offers great potential for drug delivery but also poses specific challenges, among which the short residence time of applied drugs is one of the most striking. Formulating the drug as powder and using functional excipients are strategies to improve drug absorption. As nasal powders are still the minority on the market, there is a lack of data regarding their characterisation. This work aims at the characterisation of selected fillers (mannitol, microcrystalline cellulose) and mucoadhesives (pectin, chitosan glutamate, hydroxypropyl cellulose) with a set of methods that allows distinguishing their influences on dissolution and permeation of drugs, and on the viscoelasticity of the nasal fluid and thus the nasal residence time. Rheological studies revealed a potential of undissolved particles to prolong the residence time by increasing the elasticity of the nasal fluid. The assessment of drug dissolution showed a decreased dissolution rate in presence of insoluble or gelling excipients, which can be beneficial for drugs with low permeability, since embedded drugs are cleared slower than plain solutions. Drug permeation as important factor for the selection of excipients was evaluated with an RPMI 2650 cell model. Distinguishing the effects of excipients enables an effective selection of the most promising substances.
鼻腔生理学为药物输送提供了巨大的潜力，但也带来了特定的挑战，其中应用药物的短驻留时间是最引人注目的挑战之一。将药物制成粉末并使用功能性赋形剂是提高药物吸收的策略。由于鼻腔粉末在市场上仍然占少数，因此缺乏关于其特性的资料。这项工作旨在对选定的填充剂（甘露醇、微晶纤维素）和粘膜粘附剂（果胶、壳聚糖谷氨酸、羟丙基纤维素）进行特性研究，采用一系列方法可以区分它们对药物溶解和渗透以及鼻腔液的粘弹性和鼻腔驻留时间的影响。流变学研究表明，未溶解的颗粒具有通过增加鼻腔液的弹性来延长驻留时间的潜力。药物溶解的评估表明，在存在不溶性或胶凝赋形剂的情况下，药物的溶解速率降低，这对于渗透性低的药物是有益的，因为嵌入的药物比纯溶液清除得更慢。作为赋形剂选择的重要因素的药物渗透，使用 RPMI 2650 细胞模型进行了评估。区分赋形剂的影响可以有效地选择最有前途的物质。
