Albendazole solution formulation via vesicle-to-micelle transition of phospholipid-surfactant aggregates

Abstract

A new albendazole delivery system with high drug load and low toxicity of the materials used was developed. The high solubility of albendazole was explained with vesicle-to-micelle transition due to the larger interfacial curvature preferred for albendazole solubilization locus.

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.…”

“…The interaction is enhanced by the 2+ charge of itraconazole at these conditions. The combination of appropriate surfactant and pH, leading to significant increase in drug solubility due to electrostatic attraction was observed also for other poorly water-soluble drugs, such as albendazole [46] and ibuprofen [60,61]. Further analysis of the data showed an additional, pH independent effect of the surfactant hydrophilic head groups on itraconazole solubilization.…”

“…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].…”

“…To check if similar results can be obtained with surfactants with better biocompatibility, experiments were performed with mixtures of the surfactant AOT (sodium docusate) and different phospholipids. This surfactant was chosen due to the following reasons: (1) it has low toxicity (it is allowed for use in parenteral preparations [54]), (2) it is negatively charged and (3) it has been shown to form aggregates with very high drug solubilization capacity when combined with phospholipids [46]. Negatively charged phospholipids of the phosphatidylglycerol type with different hydrophobic chain length were mixed with AOT at a ratio of 1:1, which was previously shown to provide high solubilization capacity for albendazole [46].…”

“…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.…”