Thiolated hydroxypropyl-β-cyclodextrin as mucoadhesive excipient for oral delivery of budesonide in liquid paediatric formulation

Publication date: Available online 7 November 2019Source: International Journal of PharmaceuticsAuthor(s): Valentino Laquintana, Mulazim Hussain Asim, Angela Lopedota, Annalisa Cutrignelli, Antonio Lopalco, Massimo Franco, Andreas Bernkop-Schnürch, Nunzio DenoraAbstractBudesonide (BUD) is a low water soluble (S0 = 5.028·10-5 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 (SHP- β CD = 4.3·10-3 M; K1:1 = 861.11 M-1), a mucoadhesive thiolated HP- β CD (HP- β CD-SH) was synthesized and characterized by mass spectroscopy, 1H- and 13C-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 (SHP- β -CD-SH = 10.9·10-3 M; K1:1 = 2013.52 M-1), which increases its permanence on the target site as proved by mucoadhesive studies on porcine oes...
Source: International Journal of Pharmaceutics - Category: Drugs & Pharmacology Source Type: research