TY - JOUR
T1 - Self-assembling properties of ionisable amphiphilic drugs in aqueous solution
AU - Efthymiou, Christina
AU - Bergström, L. Magnus
AU - Pedersen, Jannik Nedergaard
AU - Pedersen, Jan Skov
AU - Hansson, Per
N1 - Publisher Copyright:
© 2021 Elsevier Inc.
PY - 2021/10
Y1 - 2021/10
N2 - 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).
AB - 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).
KW - Amphiphilic drugs
KW - Cryo-TEM
KW - Dynamic light scattering (DLS)
KW - Micelles
KW - Self-assembly
KW - Small-angle x-ray scattering (SAXS)
KW - SYSTEM
KW - IONIZATION-CONSTANTS
KW - MICELLES
KW - SOLUBILITIES
KW - NONIONIC SURFACTANT
KW - GROWTH-BEHAVIOR
KW - ASSOCIATION
KW - ANGLE NEUTRON-SCATTERING
KW - 2ND CMC
KW - WATER
UR - http://www.scopus.com/inward/record.url?scp=85106549775&partnerID=8YFLogxK
U2 - 10.1016/j.jcis.2021.05.049
DO - 10.1016/j.jcis.2021.05.049
M3 - Journal article
C2 - 34049025
AN - SCOPUS:85106549775
SN - 0021-9797
VL - 600
SP - 701
EP - 710
JO - Journal of Colloid and Interface Science
JF - Journal of Colloid and Interface Science
ER -