DefinePK

Abstract

Background: Ivermectin, a Biopharmaceutical Classification System (BCS) Class II drug, exhibits high permeability but poor aqueous solubility, leading to limited and variable oral bioavailability. Enhancing its dissolution profile is critical for optimizing therapeutic efficacy in parasitic infections. The liquisolid technique, which employs non-volatile solvents and optimized excipients, has emerged as a promising approach for improving the solubility and dissolution of hydrophobic drugs.
Objective: The study aimed to develop and evaluate liquisolid formulations of ivermectin to improve solubility, dissolution behavior, and overall pharmaceutical performance compared to conventional tablets.
Methods: Pure ivermectin and commercial tablets were used alongside microcrystalline cellulose as carrier, colloidal silicon dioxide as coating material, and sodium starch glycolate as disintegrant. Non-volatile solvents including propylene glycol, polyethylene glycol, glycerol, and Tween-80 were tested, with a PG/Tween-80 (1:1) mixture providing maximum solubility. Pre-formulation studies assessed solubility, flow properties, and compressibility. Tablets were prepared by direct compression and evaluated for hardness, friability, tensile strength, disintegration, and content uniformity. UV-visible spectrophotometry at λmax 244 nm was used for drug quantification, while dissolution studies were conducted in 0.1N HCl at 37°C. Stability testing was performed at 25°C and 75% relative humidity for six months.
Results: Ivermectin showed very low solubility in water (<10 mg/mL). Propylene glycol achieved 120 mg/mL, polyethylene glycol 60 mg/mL with precipitation, while PG/Tween-80 solubilized 240 mg/mL after 50 minutes vortexing and 40 minutes sonication. Liquisolid formulations exhibited higher Carr’s index values (30.0–36.5%) compared to conventional mixtures (20.0–25.7%), reflecting poorer flow. Tensile strength increased from 0.75 to 3.6 kg/mm² with higher CSD surface area, but disintegration times remained within pharmacopeial limits (30 seconds–3 minutes). Dissolution was markedly improved, with liquisolid tablets releasing significantly more drug in 0.1N HCl compared to conventional tablets. Stability studies confirmed retention of dissolution and drug content over six months.
Conclusion: The liquisolid technique effectively enhanced the solubility and dissolution of ivermectin, supporting its potential for industrial application. This approach offers a scalable strategy for improving oral bioavailability and patient compliance in the treatment of parasitic diseases.