# Bioavailability of Thymol Incorporated into Gastro-Resistant Self-Emulsifying Pellets in Rabbits

## TL;DR

This study shows that a new thymol formulation improves its absorption in rabbits by protecting it from stomach degradation and releasing it in the small intestine.

## Contribution

A gastro-resistant self-emulsifying pellet formulation of thymol is developed to enhance its oral bioavailability in rabbits.

## Key findings

- Thymol concentrations in the duodenal wall were significantly higher than in plasma during administration.
- Thymol accumulated in kidney and fat tissues more than in plasma and muscle.
- The formulation effectively protected thymol from gastric degradation and enabled targeted intestinal release.

## Abstract

In veterinary applications, thymol is of particular interest as a natural alternative to antibiotic growth promoters, contributing to gut health modulation, immune support and disease prevention. However, thymol’s clinical potential is significantly hindered by its poor aqueous solubility, which limits oral absorption and reduces systemic bioavailability. To overcome this limitation, we have focused our attention on thymol self-emulsifying pellets designed to improve its solubility and optimise release profiles. Thymol gastro-resistant self-emulsifying pellets effectively protected thymol from gastric degradation and enabled its targeted release and absorption in the small intestine. The stabilised thymol formulation promoted accumulation in tissue in rabbits during administration and persisted even after its withdrawal. The developed gastro-resistant thymol formulation represents a promising approach to enhance its oral bioavailability in a rabbit model.

Thymol gastro-resistant self-emulsifying pellets were used to achieve thymol targeted release on the side of the intestine with the most intensive absorption to enhance its oral bioavailability. Forty-eight rabbits (35 d of age) were divided into two groups fed with a standard diet containing gastro-resistant enteric pellets (control, CG; without thymol, initial live weight 1350.0 ± 18.0, and experimental, EG; with thymol 250 mg/kg, initial live weight 1352.0 ± 19.9 g). The experiment lasted 28 days: thymol was administered for 21 days and then withdrawn for 7 days. Thymol was significantly higher in duodenal wall (DW) than in plasma during both periods (p = 0.0053, p < 0.0001). Significant correlation was established between thymol concentration in plasma and DW during its application (rs = 0.9333, p < 0.001). Thymol was below the limit of quantitation in plasma, spleen and muscle only after its withdrawal, and its significantly higher concentration in kidney and fat than in plasma (p = 0.0182, p = 0.0003) and muscle (p = 0.0236, p = 0.0004) indicates its efficient accumulation. Thymol in gastro-resistant form prevented its degradation due to adverse conditions in the stomach and ensured its release at the site of greatest absorption in the small intestine.