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. 2019 Dec 15:572:118820.
doi: 10.1016/j.ijpharm.2019.118820. Epub 2019 Nov 7.

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

Valentino Laquintana  1 , Mulazim Hussain Asim  2 , Angela Lopedota  1 , Annalisa Cutrignelli  1 , Antonio Lopalco  1 , Massimo Franco  1 , Andreas Bernkop-Schnürch  3 , Nunzio Denora  4
Affiliations

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

Valentino Laquintana et al. Int J Pharm. .

Abstract

Budesonide (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 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.

Keywords: Budesonide; Hydroxypropyl-β-cyclodextrin; Mucoadhesion; Oral liquid formulation; Paediatric; Thiomers.

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