Soma Khezri
, Reza Ghotaslou, Kader Poturcu, Vahid Jouyban-Gharamaleki, Elaheh Rahimpour
* , Abolghasem Jouyban
Abstract
Background: Ivermectin (IVM) is a broad-spectrum antiparasitic drug used in humans and animals to treat infections like scabies, river blindness, and various worms. Derived from avermectin via fermentation, IVM contains impurities and degradation products. During pandemics like COVID-19, demand for IVM formulations surges, requiring specialized manufacturing. Classified as a Biopharmaceutics Class II drug, IVM has high permeability but low solubility, leading to poor dissolution and variable absorption, impacting efficacy. Enhancing solubility can improve bioavailability and aid in purification, crystallization, and analysis. Thus, optimizing IVM formulations is crucial for better therapeutic outcomes. Method: This work investigated the ivermectin solubility in binary mixtures of ethylene glycol and water, at a temperature range of 298.2 K to 313.2 K. A laser-based robotic system was employed to measure the solubility data. The generated solubility values were presented utilizing various thermodynamic models, such as the van't Hoff, mixture response surface, Jouyban-Acree, Jouyban-Acree-van't Hoff, and modified Wilson models. Several thermodynamic factors, including ΔG°, ΔH°, and ΔS° were also computed according to the experimental findings. Results: The results showed that in the EG -rich mixtures and proportional to temperature, the IVM solubility significantly increased. The mathematical models effectively estimated IVM solubility in binary solvents, with MRD% ranging from 5.7 to 13.7. Thermodynamic analysis revealed non-spontaneous dissolution, and endothermic reaction for IVM dissolution in the invstigated mixtures. Conclusion: These properties offered valuable insights into the energetic characteristics of the dissolution process and computed utilizing the Gibbs and van't Hoff equations.