Co-Processed Crystalline Solids of Ivermectin with Span® 60 as Solubility Enhancers of Ivermectin in Natural Oils.

ABSTRACT

Despite being discovered over five decades ago, little is still known about ivermectin. Ivermectin has several physico-chemical properties that can result in it having poor bioavailability. In this study, polymorphic and co-crystal screening was used to see if such solid-state modifications can improve the oil solubility of ivermectin. Span® 60, a lipophilic non-ionic surfactant, was chosen as co-former. The rationale behind attempting to improve oil solubility was to use ivermectin in future topical and transdermal preparations to treat a range of skin conditions like scabies and head lice. Physical mixtures were also prepared in the same molar ratios as the co-crystal candidates, to serve as controls. Solid-state characterization was performed using X-ray powder diffraction (XRPD), Fourier-transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA). The FTIR spectra of the co-crystal candidates showed the presence of Span® 60's alkyl chain peaks, which were absent in the spectra of the physical mixtures. Due to the absence of single-crystal X-ray data, co-crystal formation could not be confirmed, and therefore these co-crystal candidates were referred to as co-processed crystalline solids. Following characterization, the solid-state forms, physical mixtures and ivermectin raw material were dissolved in natural penetration enhancers, i.e., avocado oil (AVO) and evening primrose oil (EPO). The co-processed solids showed increased oil solubility by up to 169% compared to ivermectin raw material. The results suggest that co-processing of ivermectin with Span® 60 can be used to increase its oil solubility and can be useful in the development of oil-based drug formulations.