Development and in vitro evaluation of an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) loaded with an amphotericin B-monoacyl phosphatidylcholine complex for oral delivery.

Autor: Liu X; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark., Müllertz A; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark; Bioneer:FARMA, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100 Copenhagen, Denmark., Bar-Shalom D; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark., Berthelsen R; Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Universitetsparken 2, 2100, Copenhagen, Denmark. Electronic address: Ragna.berthelsen@sund.ku.dk.
Jazyk: angličtina
Zdroj: International journal of pharmaceutics [Int J Pharm] 2024 Jul 20; Vol. 660, pp. 124286. Date of Electronic Publication: 2024 May 28.
DOI: 10.1016/j.ijpharm.2024.124286
Abstrakt: Until relatively recently, the pediatric population has largely been ignored during the development of new drug products, which has led to a high level of "off-label" use of drugs in this particular population. In this study, an infant friendly self-nanoemulsifying drug delivery system (SNEDDS) was developed for oral delivery of a commonly used "off-label" drug - amphotericin B (AmB). AmB was complexed with monoacyl-phosphatidylcholine (MAPC) by lyophilization, transforming crystalline AmB into its amorphous state in the AmB-MAPC complex (APC). The APC-loaded SNEDDS (APC-SNEDDS) showed excellent self-emulsifying properties; after dispersion of the APC-SNEDDS in purified water, nanoscale emulsion droplets were formed within 1 min with a z-average size of 179 ± 1 nm. In vitro pediatric gastrointestinal (GI) digestion and dissolution results showed that the APC-SNEDDS significantly increased the amount of AmB solubilized in aqueous phase and that the precipitated AmB from the APC-SNEDDS re-dissolved faster, compared with crystalline AmB in SNEDDS (AmB-SNEDDS), the complex without the SNEDDS (APC), the physical mixture of AmB and MAPC (AmB/MAPC PM), and crystalline AmB alone (AmB). Overall, the present in vitro results suggest that integrating the APC into an infant friendly SNEDDS is a promising approach for oral delivery of AmB to young pediatric patients.
Competing Interests: Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
(Copyright © 2024 The Authors. Published by Elsevier B.V. All rights reserved.)
Databáze: MEDLINE
Externí odkaz: