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Updated: May 22, 2026

A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients
Published on: August 9, 2022
Structural transitions in cholesterol-based wormlike micelles induced by encapsulating alkyl ester oils with varying
Hala Afifi1, Göran Karlsson, Richard K Heenan
1Institute of Pharmaceutical Science, King's College London, London SE1 9NH, UK.
Abstract:
The effect of encapsulating oils on the phase behaviour and the microstructure of wormlike micelles formed by polyoxyethylene cholesteryl ether (ChEO(10)) and triethylene glycol monododecyl ether co-surfactant (C(12)EO(3)) was investigated using rheology, Cryo-TEM and small-angle neutron scattering measurements. Six alkyl ester oils bearing small, systematic variations in their molecular structure were encapsulated: ethyl butyrate (EB(24)), ethyl caproate (ECO(26)), ethyl caprylate (EC(28)), methyl enanthate (ME(17)), methyl caprylate (MC(18)) and butyl butyrate (BB(44)), where the subscripts refer to the length of the alkyl chain and fatty acid chain, respectively, on either sides of the ester link. The addition of alkyl ester oils to ChEO(10)/C(12)EO(3) solutions promotes the longitudinal growth of the surfactant aggregates into wormlike micelles possessing an elliptical cross-section, with r(minor) 31±2 Å and r(major) varying from 45 to 70 Å. At fixed alkyl chain length, oils with longer fatty acid chains were found to be more efficient in inducing wormlike micelle formation or their elongation, following the order: EC(28)>ECO(26)>EB(24). Instead, at fixed fatty acid chain length, increasing the alkyl chain has a negative effect on the longitudinal micellar growth (MC(18)>EC(28) and EB(24)>BB(44)). At high co-surfactant concentrations and in the presence of EB(24), an unusual phase of ring-like micelles was detected. Overall, the orientation of the oil molecules within the micelles enables them to act as co-surfactants with a small head-group, decreasing the average cross-section area and promoting longitudinal growth of the micelles into worms.
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