Development and optimization of lyophilized dry emulsion tablet for improved oral delivery of Ivermectin

Abstract

Ivermectin (IVM) is a widely used antiparasitic agent and has been repurposed for the treatment of COVID-19. However, its poor water solubility and low bioavailability present significant challenges, often requiring large doses for therapeutic effectiveness. This poses a burden on patients, as they need to take multiple tablets at once, which is both inconvenient and uncomfortable. This study aims to develop and optimize rapidly disintegrating lyophilized dry emulsion tablets (LDET) containing IVM using a quality by design (QbD) approach to enhance its solubility, dispersibility, wettability, and dissolution rate, thereby improving its absorption and bioavailability following oral administration. Oil-in-water (O/W) emulsions were prepared using sweet almond oil or Miglyol 840 as the oil phase, along with stabilizers. The optimal emulsion was subsequently lyophilized to produce IVMLDET. Tablets’ characteristics were assessed in vitro for their properties including solubility, disintegration, and dissolution, and in vivo in rabbits for their pharmacokinetic (PK) profile. Results indicated a remarkable 600-fold increase in IVM solubility in the optimal emulsion formulation. IVM-LDET significantly enhanced the extent and rate of dissolution compared to raw IVM and the marketed tablet, Iverzine®. Furthermore, the PK profile of IVM from LDET showed a 30 % increase in maximum plasma concentration (Cmax) and area under the curve (AUC), and reduced time to reach maximum concentration (tmax) by 4 h compared to Iverzine® tablets. In conclusion, the developed IVM-LDET formulation presents a promising therapeutic alternative to conventional oral IVM products for treating parasitic or viral infections, potentially leading to improved therapeutic outcomes and patient compliance.