Improved solubility of Ivermectin by complexation with cyclodextrins and amino-acids

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Congreso; 6ta Reunión Internacional de Ciencias Farmacéuticas (RICiFa)-Edición Aniversario 10 años-; 2021

Ivermectin (IVM) is an antiparasitic drug derived from avermectin with broad-spectrumactivity against both ectoparasites and endoparasites. IVM is used worldwide as drug of choice for thetreatment of Lymphatic Filariasis and Onchocerciasis, two neglected infectious diseases. However, itis a poorly water-soluble drug that shows unpredictable therapeutic response caused by a very loworal biodisponibility. In this study, the effect of binary and ternary systems obtained with amino-acidsand oligosaccharides were evaluated as an alternative to improve the aqueous solubility of IVM. Themost promising solubilizing excipients were selected by solubility studies, while the complexesformation constants were determined by phase solubility studies. The results revealed that the aqueoussolubility was increased with binary systems using the amino-acids arginine (ARG) and glutamicacid, and the oligosaccharides hydroxypropyl-β-cyclodextrin (HPβCD), γ-cyclodextrin (γCD) andsulfobutylether-β-cyclodextrin as ligands. The ternary systems with the combination HPβCD + ARGand γCD + ARG exhibited a synergistic effect resulting in a 11-fold and 8-fold, respectively,improvement of the aqueous solubility of IVM. Thus, these supramolecular systems exhibitedpromising properties for the developing pharmaceutical oral formulations of IVM with increasedsolubility.