Mirankó Mirella, Tóth Judit, Bartos Csilla, Ambrus Rita, Feczkó Tivadar
Institute of Materials and Environmental Chemistry, Research Centre for Natural Sciences, Magyar Tudósok Körútja 2, 1117 Budapest, Hungary.
Faculty of Engineering, Research Institute of Biomolecular and Chemical Engineering, University of Pannonia, Egyetem u. 10, 8200 Veszprém, Hungary.
Pharmaceutics. 2023 Jan 18;15(2):317. doi: 10.3390/pharmaceutics15020317.
Antihistamines such as levocetirizine dihydrochloride (LC) are commercially used in oral tablets and oral drops to reduce allergic symptoms. In this study, LC was nano-spray-dried using three mucoadhesive polymers and four cyclodextrin species to form composite powders for nasal administration. The product was composed of hydroxypropyl methylcellulose polymer, including LC as a zwitterion, after neutralization by NaOH, and XRD investigations verified its amorphous state. This and a sulfobutylated-beta-cyclodextrin sodium salt-containing sample showed crystal peaks due to NaCl content as products of the neutralization reaction in the solutions before drying. The average particle size of the spherical microparticles was between 2.42 and 3.44 µm, except for those containing a polyvinyl alcohol excipient, which were characterized by a medium diameter of 29.80 µm. The drug was completely and immediately liberated from all the samples at pH 5.6 and 32 °C; i.e., the carriers did not change the good dissolution behavior of LC. A permeability test was carried out by dipping the synthetic cellulose ester membrane in isopropyl myristate using modified horizontal diffusion cells. The spray-dried powder with β-cyclodextrin showed the highest permeability (188.37 µg/cm/h), as this additive was the least hydrophilic. Products prepared with other cyclodextrins (randomly methylated-beta-cyclodextrin, sulfobutylated-beta-cyclodextrin sodium salt and (hydroxypropyl)-beta-cyclodextrin) showed similar or slightly higher penetration abilities than LC. Other polymer excipients resulted in lower penetration of the active agent than the pure LC.
抗组胺药如盐酸左西替利嗪（LC）在商业上用于口服片剂和口服液滴剂以减轻过敏症状。在本研究中，使用三种粘膜粘附聚合物和四种环糊精种类对LC进行纳米喷雾干燥，以形成用于鼻腔给药的复合粉末。该产品由羟丙基甲基纤维素聚合物组成，在经NaOH中和后，LC作为两性离子包含其中，X射线衍射研究证实其为无定形状态。该样品以及含磺丁基-β-环糊精钠盐的样品由于干燥前溶液中中和反应产物NaCl的含量而显示出晶体峰。球形微粒的平均粒径在2.42至3.44μm之间，但含有聚乙烯醇辅料的微粒除外，其平均直径为29.80μm。在pH 5.6和32°C条件下，药物从所有样品中完全且立即释放；即载体并未改变LC良好的溶解行为。使用改良的水平扩散池，通过将合成纤维素酯膜浸入肉豆蔻酸异丙酯中进行渗透性测试。含β-环糊精的喷雾干燥粉末显示出最高的渗透率（188.37μg/cm/h），因为这种添加剂亲水性最低。用其他环糊精（随机甲基化-β-环糊精、磺丁基-β-环糊精钠盐和（羟丙基）-β-环糊精）制备的产品显示出与LC相似或略高的渗透能力。其他聚合物辅料导致活性剂的渗透率低于纯LC。
