Development of microemulsion based topical ivermectin formulations: Pre-formulation and formulation studies

• Published in: Colloids and surfaces, B, Biointerfaces B, Biointerfaces, 2020-05, Vol.189, p.110823-110823, Article 110823
• Main Authors: Das, Surajit, Lee, Sie Huey, Chia, Vernissa Dilys, Chow, Pui Shan, Macbeath, Calum, Liu, Yuanjie, Shlieout, George
• Format: Article
• Language: English
• Subjects: Antiparasitic Agents - chemistry; Butyrates - chemistry; Drug Compounding; Drug Delivery Systems; Emulsions - chemistry; Ivermectin; Ivermectin - chemistry; Microemulsion; Particle Size; Permeation; Phase diagram; Solubility; Stability; Surface Properties; Tea Tree Oil - chemistry
• ISSN: 0927-7765; 1873-4367
• DOI: 10.1016/j.colsurfb.2020.110823

[Display omitted] •Tea tree oil and ethyl butanoate were suitable oils for ivermectin microemulsions.•Type and % of co-surfactants showed huge influence on microemulsion area (1φ).•Ivermectin-loaded stable microemulsion formulations were successfully formulated.•Ivermectin permeation of was faster from microemulsion gels than Soolantra cream. The aim of this work was to develop microemulsions and microemulsion gels which can be used as vehicles for the topical delivery of ivermectin. Tea tree oil and ethyl butanoate were found to be suitable for ivermectin-loaded microemulsion formulations due to the higher solubility of ivermectin in these two oils than other tested oils. The pseudo-ternary phase diagrams were constructed based on these selected oils and combination of different surfactant/co-surfactant at different ratios. Ivermectin-loaded stable microemulsions and microemulsion gels were successfully formulated based on the selected compositions from the phase diagrams. Ivermectin-loaded microemulsions showed spherical nano-droplets dispersed in the continuous phase (via cryogenic field emission scanning electron microscope image) and the particle size was less than 100 nm (via dynamic light scattering measurement). Ethyl butanoate based microemulsion appeared to be the best microemulsion formulation considering the stability and permeation profiles while tea tree oil based microemulsion showed the best stability profile. Overall, microemulsion gel formulations exhibited better stability profiles than their microemulsion counterparts. All microemulsion gel formulations demonstrated significantly faster in vitro membrane permeation (release) rate of ivermectin than Soolantra cream (reference marketed product by Galderma, USA).The developed microemulsion and microemulsion gel formulations appear to be promising vehicles for topical delivery of ivermectin.