Micellar solubilization of poorly water-soluble drugs: effect of surfactant and solubilizate molecular structure

Abstract

Highest drug solubility can be obtained by using surfactants molecules with long chain length coupled with hydrophilic head group that provides additional drug-surfactant interactions (i.e. ion-dipole) in the micelles.

Solubilization of itraconazole by surfactants and phospholipid-surfactant mixtures: interplay of amphiphile structure, pH and electrostatic interactions

“…Although the same effect has been observed also for the weak base albendazole [46] and for neutral drugs, such as progesterone [47], fenofibrate and danazol [45], the unifying mechanism is still unclear. One possible explanation is that the smaller size of the sulfate head group facilitates the packing of the drug and surfactant molecules in the micelles, viz.…”

“…a steric effect. Such explanation has already been proposed to explain the significant decrease of the solubilization capacity when ethylene oxide units are added between the lauroyl chain and the sulfate head group for other drugs [45][46][47]. Another possibility is that ion-dipole interactions contribute to the solubilization capacity, as has been shown for progesterone [47] and danazol [45].…”

“…Such explanation has already been proposed to explain the significant decrease of the solubilization capacity when ethylene oxide units are added between the lauroyl chain and the sulfate head group for other drugs [45][46][47]. Another possibility is that ion-dipole interactions contribute to the solubilization capacity, as has been shown for progesterone [47] and danazol [45]. Molecular dynamics simulations might provide further insight on the mechanism of this interesting ef fect, however, such efforts have not been undertaken yet, due to the significant computational resources required to model solubilization in micellar systems that include multiple surfactant and drug pairs.…”

“…Nonetheless, the link between their molecular structure and the drug solubilization capacity is still largely unexplored. For example, although the increased solubilization capacity with increasing surfactant hydrophobic chain length has been well documented for many types of drugs [45][46][47][48][49][50], there are also reports of the opposite behavior, with no clear mechanistic explanation [51]. The surfactant hydrophilic head group can also affect dramatically drug solubility [45][46][47][48][49]52], and while in some cases the major drivers for solubilization have been identified as electrostatic [46] or ion-dipole interactions [45,47], there is still not enough information to allow in-depth mechanistic understanding on the molecular level.…”

The Accumulated Effect of the Number of Ethylene Oxide Units and/or Carbon Chain Length in Surfactants Structure on the Nano-Micellar Extraction of Flavonoids

“…The other authors had similar doubts. For example, Vinarov et al [30] studied the solubilization of highly hydrophobic drugs in surfactant solutions. Studies illustrated that surfactant molecular structure could have a different effect on the solubilization capacity, but it depends mostly on the type of drug.…”