Design and preparation of nanostructures based on Krafft point of nonionic amphiphiles for delivery of poorly water-soluble compounds

Abstract

Micellar solubilization can effectively dissolve low water-soluble compounds in aqueous environment, however, the micellar systems are not able to withstand dilution and maintain solubilization of poorly water-soluble drugs below critical micelle concentration. To overcome the drawbacks of conventional micellar solubilization, nonionic polyoxyethylated surfactants with Krafft points at or higher than body temperature were chosen to create novel micelle-based nanostructures as a delivery vehicle for poorly water-soluble compounds. A technique "thermo-spray process" was developed for the preparation of the nanostructures-containing formulation, in which the drug-containing micelle solution was first prepared and maintained at the elevated temperature above the Krafft point of the surfactant, then spray dried to solidify the obtained micelle-like nanostructure at room temperature. Lactose was used as an excipient to embed the nanostructures in the thermo-spray products. Water insoluble spherical nanoparticles with size range from 80 to 250 nm were obtained after reconstitution of the product at the temperature lower than Krafft point. When paclitaxel was used as model drug, the micelle-like nanostructures exhibited similar drug entrapment efficiency, solubility enhancement and drug release facilitation as conventional micelles, but provided lower critical micellar concentration at body temperature, and good encapsulation stability upon storage and dilution. These findings indicated that the developed thermo-spray product can serve as a promising delivery platform for drugs with low aqueous solubility.

Keywords: Krafft point; Micelle-based nanostructures; Nonionic polyoxyethylated surfactants; Poorly aqueous soluble compounds; Thermal-spray process.