Microemulsion systems to enhance the transdermal permeation of ivermectin in dogs: A preliminary in vitro study

• Published in: Research in veterinary science Vol. 133; pp. 31 - 38
• Main Authors: Machado, Micheline, Dantas, Isabella Lima, Galvão, Juliana Gouveia, Lima, Alyne Dantas, Gonsalves, Joyce Kelly Marinheiro da Cunha, Almeida, Ellen Denise Prado, de Araujo, Guilherme Rodolfo Souza, Leal, Leila Bastos, Sarmento, Victor Hugo Vitorino, Nunes, Rogéria Souza, Lira, Ana Amélia Moreira
• Format: Journal Article
• Language: English
• Published: England Elsevier Ltd 01-12-2020; Elsevier Limited
• Subjects: Administration, Cutaneous; Animal models; Animals; Antiparasitic agents; Antiparasitic Agents - administration & dosage; Antiparasitic Agents - metabolism; Canine skin; Dogs; Drug delivery; Drug delivery system; Drugs; Ectoparasites; Electric Conductivity; Emulsions; Endoparasites; Experiments; Female; Glycerides - administration & dosage; Ivermectin; Ivermectin - administration & dosage; Ivermectin - metabolism; Male; Medical research; Microemulsion; Microemulsions; Myristates - administration & dosage; Nanotechnology; Penetration; Permeability; Phase diagrams; Polysorbates - administration & dosage; Retention; Rheological properties; Rheology; Scattering, Small Angle; Sensors; Skin; Skin - metabolism; Surface-Active Agents - administration & dosage; Surfactants; Transdermal; Veterinary medicine; Viscosity; Water - administration & dosage; X-Ray Diffraction - veterinary; Brazil; Transdermal; Canine skin; Microemulsion; Drug delivery system; Nanotechnology
• ISSN: 0034-5288; 1532-2661
• DOI: 10.1016/j.rvsc.2020.08.009

This study aims to evaluate the influence of the phase behavior of microemulsions in the transdermal administration (“spot-on”) of ivermectin, an antiparasitic drug widely used in the treatment of endoparasites and ectoparasites in dogs. In this regard, pseudoternary phase diagrams composed of water (aqueous phase), isopropyl myristate (oil phase), tween 80 (surfactant) and labrasol (cosurfactant) were obtained in a different surfactant: cosurfactant (S:CS) ratios. S:CS in 1:3 ratio presented a larger region of microemulsion formation and three microemulsions were selected from it and characterized. Subsequently, in vitro permeation and retention studies were conducted using canine skin as membrane. SAXS, rheology and conductivity data were employed to confirm the phase behavior of the microemulsions (w/o, bicontinuous or o/w). The cutaneous permeation and retention tests showed that the w/o microemulsion, followed by bicontinuous microemulsion, resulted in a higher amount of drug permeated through canine skin, suggesting better transdermal permeation. On the other hand, o/w microemulsion resulted in a higher amount of drug accumulated into the skin, suggesting better topical activity. Thus, it can be concluded that phase behavior of microemulsions influenced the drug permeation in the canine skin differently from other animal models. Microemulsions, especially w/o and bicontinuous, can be promising vehicles regarding the transdermal delivery of ivermectin.
•Ivermectin microemulsions have been successfully obtained.•Phase behavior of microemulsions have influenced the skin permeation of the drug.•W/O and bicontinuous microemulsions showed better transdermal effect.•O/W microemulsion resulted in higher amount of drug accumulated into the skin.•O/W microemulsion showed better topical effect.•Microemulsions may be promising formulations known as “spot-on” of ivermectin.