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Self-assembling properties of ionisable amphiphilic drugs in aqueous solution

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  • Christina Efthymiou, Uppsala Universitet, Sverige
  • ,
  • L. Magnus Bergström, Uppsala Universitet, Sverige
  • ,
  • Jannik Nedergaard Pedersen
  • ,
  • Jan Skov Pedersen
  • Per Hansson, Uppsala Universitet, Sverige

Hypothesis: Common amphiphilic drug molecules often have a more rigid nonpolar part than conventional surfactants. The rigidity is expected to influence the self-assembling properties and possibly give rise to aggregation patterns different from that of regular surfactants. Experiments: We have investigated self-assembling properties of the hydrochloride salts of adiphenine (ADP), pavatrine (PVT), and amitriptyline (AMT) at concentrations up to 50 wt% using small-angle x-ray scattering, dynamic light scattering, cryo-transmission electron microscopy, and surface tension measurements. Findings: All drugs form small micelles of oblate spheroidal shape at concentrations above the critical micelle concentrations (CMC). The micelles grow weakly in size up to about 20 wt%, where the aggregation number reaches a maximum followed by a slight decrease in size at higher drug concentrations. We observe a correlation between the decrease in micelle size at high concentrations and an increasing charge of the micelles, as the degree of ionization increases with increasing drug concentration and decreasing pH. In contrast to what has previously been reported, the aggregation behavior of all studied drugs resembles the closed association behavior of conventional surfactants with a short aliphatic chain as hydrophobic tail group i.e. the micelles are always small in size and lack a second CMC. CMC values were determined with surface tension measurements, including also lidocaine hydrochloride (LDC) and chlorpromazine hydrochloride (CHL).

Original languageEnglish
JournalJournal of Colloid and Interface Science
Pages (from-to)701-710
Number of pages10
Publication statusPublished - Oct 2021

Bibliographical note

Publisher Copyright:
© 2021 Elsevier Inc.

    Research areas

  • Amphiphilic drugs, Cryo-TEM, Dynamic light scattering (DLS), Micelles, Self-assembly, Small-angle x-ray scattering (SAXS), SYSTEM, IONIZATION-CONSTANTS, MICELLES, SOLUBILITIES, NONIONIC SURFACTANT, GROWTH-BEHAVIOR, ASSOCIATION, ANGLE NEUTRON-SCATTERING, 2ND CMC, WATER

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