Enhanced Dissolution of Amphotericin B through Development of Amorphous Solid Dispersions Containing Polymer and Surfactants.

Autor:	Smith-Craven MM; Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, KS 66047, USA. Electronic address: mikaylaos159@ku.edu., Dening TJ; Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, KS 66047, USA., Basra AK; Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, KS 66047, USA., Hageman MJ; Department of Pharmaceutical Chemistry, School of Pharmacy, The University of Kansas, Lawrence, KS 66047, USA. Electronic address: mhageman@ku.edu.
Jazyk:	angličtina
Zdroj:	Journal of pharmaceutical sciences [J Pharm Sci] 2024 Aug; Vol. 113 (8), pp. 2454-2463. Date of Electronic Publication: 2024 May 01.
DOI:	10.1016/j.xphs.2024.04.031
Abstrakt:	Amphotericin B (AmB) is the gold standard for antifungal therapy; however, its poor solubility limits its administration via intravenous infusion. A promising formulation strategy to achieve an oral formulation is the development of amorphous solid dispersions (ASDs) via spray-drying. Inclusion of surfactants into ASDs is a newer concept, yet it offers increased dissolution opportunities when combined with a polymer (HPMCAS 912). We developed both binary ASDs (AmB:HPMCAS 912 or AmB:surfactant) and ternary ASDs (AmB:HPMCAS 912:surfactant) using a variety of surfactants to determine the optimal surfactant carbon chain length and functional group for achieving maximal AmB concentration during in vitro dissolution. The ternary ASDs containing surfactants with a carbon chain length of 14 ± 2 carbons and a sulfate functional group increased the dissolution of AmB by 90-fold compared to crystalline AmB. These same surfactants, when added to a binary ASD, however, were only able to achieve up to a 40-fold increase, alluding to a potential interaction occurring between excipients or excipient and drug. This potential interaction was supported by dynamic light scattering data, in which the ternary formulation produced a single peak at 895.2 dnm. The absence of more than one peak insinuates that all three components are interacting in some way to form a single structure, which may be preventing AmB self-aggregation, thus improving the dissolution concentration of AmB. 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 Inc. All rights reserved.)
Databáze:	MEDLINE
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