A wide range of excipients, such as solid and liquid lipids, surfactants and co-surfactants, have been evaluated by solubility studies to identify the best components to develop a Benznidazole formulation. Additionally, compatibility studies have been carried out to ensure its stability so that there is no phase separation in the formulation.
In this project Solid Lipid Nanoparticles (SLNs), Nanostructurated Lipid Carriers (NLCs) and Lipid Nanoemulsions (LNEs) has been investigated to identify the best lipid matrix (solid, liquid and/or hybrid) for Benznidazole formulation. Several nanoparticle preparation approaches, including high energy (sonication, high-amplitude ultrasonication and jet dispersers) and low energy (spontaneous emulsification and phase inversion temperature - PIT) methodologies, have been explored to identify the most suitable one for this case.
Most of the nanoparticles prepared have been physically characterized by Dynamic Light Scattering (DLS) to determine their size, polydispersity index and zeta potential. Also, Entrapment Efficiency studies has been carried out and Drug Load have been calculated . Some nanoparticles have been purified by dialysis cassettes and others also lyophilized with or without cryoprotectant. Besides, reconstitution studies have been carried out using DLS, based on the evaluation of different solvents and dilutions, of the lyophilized nanoparticles to identify the best conditions to recover their physical properties once they are in solution again. Furthermore, crystallinity studies have been performed for these lyophilized nanoparticles through Differential Scanning Calorimetry. In addition, stability studies have been develop evaluating its size and polydispersity index again in different periods of time.
To date, more than 300 nanoparticles have been developed and, specifically, the LNE prepared using the PIT method have shown most of the physical properties necessary to reach the lymphatic system. Furthermore, to identify the best ratio of excipients in the formulation, ternary phase diagrams have been obtained, showing clear and fairly homogeneous lipid nanoemulsions. In vivo tests will soon be carried out to confirm the project hypothesis.
The final results of this project will be published in high-impact journals and will be presented at conferences specialized in drug delivery systems and medical chemistry.
