Enhanced oral bioavailability of 2,6-diisobornyl-4-methylphenol via microemulsion drug delivery system

IBP (2,6-diisobornyl-4-methylphenol) is a small drug molecule with significant cardio- and neuroprotective properties. This work aimed to develop a microemulsion dosage form loaded with IBP in order to enhance its oral bioavailability. For this purpose, various oils, including fatty acids, and surfactants from a range of ethoxylated fatty alcohols were screened based on the solubility and solubilization studies. The optimized composition was selected using a pseudo-ternary phase diagram and consisted of the following components: sunflower oil fatty acids, C₁₂E₂₄/ethanol mixture (1: 1, w/w) and water (5: 35: 60, w/w/w, respectively). The proposed formulation was fully characterized by dynamic light scattering, transmission electron microscopy, viscosity studies, stability assessments and antiradical activity testing. Interestingly, the particle size of the fifty-fold diluted microemulsion differed after measurement by dynamic light scattering (3.48 ± 0.90 nm) and transmission electron microscopy (31.57 ± 8.16 nm). <i>In vivo</i> pharmacokinetic studies in rats demonstrated that the developed microemulsion significantly improved the oral bioavailability of IBP compared to the free drug in starch and oil formulations. Additionally, a more active entry of IBP into the lymphatic system was observed when it was administered in microemulsion form. Also, we observed a significant <i>in vitro</i> release of IBP from the microemulsion across the intestinal membrane. These results provide insights into the physicochemical properties of the developed microemulsion system and the mechanisms of absorption of the loaded drug, enabling the prediction of the dosage regimen and therapeutic efficacy.