Abstract

FORMULATION OPTIMIZATION AND CHARACTERIZATION OF SELF-MICROEMULSIFYING DRUG DELIVERY SYSTEM OF IVERMECTIN

Arudra Chenna Kesava*, Yerragopu Nagasurekha, Sreevidya Puvvala, Vasu Naik V., Srirekha Malakapurapu

ABSTRACT

The present study was undertaken to formulate, optimize and characterize an ivermectin-loaded self-microemulsifying drug delivery system (SMEDDS) with the objective of improving the dissolution performance of this poorly water-soluble, highly lipophilic drug. Ivermectin is described in the supplied report as a Biopharmaceutics Classification System (BCS) class II drug, for which poor aqueous solubility can limit dissolution and oral systemic availability. Lipid-based delivery systems can maintain poorly soluble drugs in a solubilized state and, after dilution in gastrointestinal fluid, generate fine oil-in-water dispersions with a large interfacial area. Preliminary screening showed the highest ivermectin solubility among the tested vehicles in Tween 80 (984.25 μg/mL), rose oil (912.00 μg/mL) and PEG 400 (828.22 μg/mL). A ternary phase-diagram approach was used to identify the microemulsion region,followed by a three-factor D-optimal design in which oil, surfactant and co-surfactant were the formulation variables. Self-emulsification time, globule size and percent transmittance were selected as responses. The design identified an optimized composition of approximately 10.00% oil, 48.00% surfactant and 42.47% co-surfactant. The predicted responses were 26.87 s self-emulsification time, 176.13 nm globule size and 98.62% transmittance, while the experimentally observed values were 20.54 s, 158.2 nm and 99.25%, respectively. The optimized formulation showed a refractive index of 1.33390, pH 6.68 ± 0.03, drug content 99.54%, no phase separation or drug precipitation after 48 h following 100-fold dilution, Grade A dispersibility in water, 0.1 N HCl and phosphate buffer pH 6.8, viscosity of 84.0 ± 0.25 cP before dilution and 0.8872 cP after dilution, zeta potential −0.3 mV and PDI 0.087. In vitro release reached 99.98% at 120 min, compared with 53.71% release from pure drug at the same time and 75.26% from the marketed formulation. Release fitting gave R² values of 0.9879 for zero-order, 0.9297 for first-order, 0.9614 for Higuchi, 0.8508 for Hixson–Crowell and 0.8932 for Korsmeyer–Peppas; the reported Peppas exponent of 0.718 indicated anomalous/non-Fickian transport. Accelerated stability testing at 40 ± 2°C/75 ± 5% RH for 90 days showed no visible change, no phase separation or precipitation, and drug content decreased from 101.53% to 98.50%. Overall, the supplied data demonstrate that ivermectin SMEDDS substantially improved in vitro dissolution and showed acceptable short-term physicochemical stability.

Keywords: Ivermectin; self-microemulsifying drug delivery system; SMEDDS; lipid-based drug delivery; D-optimal design; dissolution enhancement; poorly water-soluble drug; globule size; zeta potential.