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Impact of surfactants on solution behavior and membrane transport of amorphous solid dispersions.

Authors :
Alhalaweh A
Sayed ME
Kovac L
Bergström CAS
Source :
Journal of pharmaceutical sciences [J Pharm Sci] 2025 Jan; Vol. 114 (1), pp. 458-467. Date of Electronic Publication: 2024 Nov 02.
Publication Year :
2025

Abstract

The purpose of the study was to develop an amorphous solid dispersion (ASD) of a poorly soluble compound (AK100) and investigate the impact of different surfactants on its dissolution, supersaturation and membrane transport. The solubility of the AK100 was determined in crystalline and amorphous form in the absence and presence of three surfactants at different concentrations: sodium dodecyl sulphate (SDS), polysorbate 80 (PS80) and D-α-tocopherol polyethylene glycol succinate (TPGS). The relation between solubility and surfactant solubilization was evaluated using a computational model. The ASD powder was prepared by solvent evaporation for non-sink dissolution experiments with and without the pre-dissolved surfactants. A transport study with Caco-2 cells was conducted to evaluate the impact of surfactants-based formulation on membrane transport. Both the corresponding crystalline and amorphous solubility of AK100 increased linearly as a function of the surfactant concentrations. The supersaturation was maintained for at least three hours in absence of surfactant and in presence of TPGS, whereas supersaturation declined with SDS and PS80. As expected, the membrane flux of the AK100 was higher for the ASD than for the crystalline powder, and further increased with increased concentration of TPGS. The supersaturation ratio based on the activity-based calculation from Caco-2 cells study was always higher than that of the concentration-based one for the amorphous and crystalline forms of AK100. This study shows how additional solubilizing excipients during formulation development can improve the resulting dissolution and phase behavior of supersaturated drug solution.<br />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.<br /> (Copyright © 2024 The Authors. Published by Elsevier Inc. All rights reserved.)

Details

Language :
English
ISSN :
1520-6017
Volume :
114
Issue :
1
Database :
MEDLINE
Journal :
Journal of pharmaceutical sciences
Publication Type :
Academic Journal
Accession number :
39491671
Full Text :
https://doi.org/10.1016/j.xphs.2024.10.023