Department of Pharmacy - Pharmaceutical Sciences, University of Bari "Aldo Moro", 70125 Bari, Italy.
Center for Chemistry and Biomedicine, Department of Pharmaceutical Technology, Institute of Pharmacy, University of Innsbruck, Innrain 80/82, 6020 Innsbruck, Austria; Department of Pharmaceutics, Faculty of Pharmacy, University of Sargodha, 40100 Sargodha, Pakistan.
Int J Pharm. 2019 Dec 15;572:118820. doi: 10.1016/j.ijpharm.2019.118820. Epub 2019 Nov 7.
Budesonide (BUD) is a low water soluble (S = 5.028·10 M) corticosteroid used as preferred therapy for the treatment of Eosinophilic Esophagitis (EoE), a chronic allergic-immune condition with an increased incidence in the paediatric population. Currently there are no commercial medicines indicated for EoE, and, therefore, in the hospital pharmacy the BUD is extemporaneously formulated as viscous oral suspension at the initial dose of 1-2 mg per day for children, highlighting the need of a mucoadhesive drug delivery system (MDDS) that adheres to the site of action and prolongs the therapeutic activity of the administered drug. Considering the ability of hydroxypropyl-β-cyclodextrin (HP-β-CD, 100 mM) to increase the water solubility of BUD (Sβ = 4.3·10 M; K = 861.11 M), a mucoadhesive thiolated HP-β-CD (HP-β-CD-SH) was synthesized and characterized by mass spectroscopy, H- and C NMR techniques. Phase-solubility studies demonstrated the capability of HP-β-CD-SH (100 mM) to form a reversible water soluble inclusion complex with BUD (Sβ = 10.9·10 M; K = 2013.52 M), which increases its permanence on the target site as proved by mucoadhesive studies on porcine oesophagus mucosa. HP-β-CD-SH might be a useful MDDS for the pharmacist to prepare BUD oral liquid formulations at the recommended doses, with pH values below 5, which guarantee the chemical stability of the new mucoadhesive excipient.
布地奈德（BUD）是一种水溶性低（S = 5.028·10 M）的皮质类固醇，常用于治疗嗜酸性食管炎（EoE），这是一种慢性过敏免疫性疾病，在儿科人群中的发病率增加。目前没有专门用于治疗 EoE 的商业药物，因此，在医院药房，BUD 被临时配制为粘性口服混悬液，初始剂量为儿童每天 1-2 mg，这突出了需要一种具有黏膜黏附性的药物传递系统（MDDS），以粘附在作用部位并延长给予药物的治疗活性。考虑到羟丙基-β-环糊精（HP-β-CD，100 mM）能够提高 BUD 的水溶性（Sβ = 4.3·10 M；K = 861.11 M），合成了一种具有黏膜黏附性的巯基化 HP-β-CD（HP-β-CD-SH），并通过质谱、H-和 C NMR 技术对其进行了表征。相溶解度研究表明，HP-β-CD-SH（100 mM）能够与 BUD 形成可逆水溶性包合络合物（Sβ = 10.9·10 M；K = 2013.52 M），这增加了其在靶部位的持久性，通过对猪食道黏膜的黏膜黏附研究得到了证明。HP-β-CD-SH 可能是药剂师用于制备推荐剂量下的 BUD 口服液体制剂的有用 MDDS，制剂的 pH 值低于 5，这保证了新的黏膜黏附性赋形剂的化学稳定性。
