In vivo pharmacokinetic and toxicity evaluation of Andrographis paniculata extract-loaded self-microemulsifying drug...

This study aimed to conduct a comprehensive in vivo assessment of a novel Andrographis paniculata (AP) extract-loaded self-microemulsifying drug delivery system (AP-SMEDDS), focusing on enhancing the oral bioavailability of andrographolide (AN) and establishing its preclinical safety profile. A comparative pharmacokinetic study was performed in rats to evaluate AP-SMEDDS against a conventional AP powder suspension. Concurrently, a 28-day repeated-dose oral toxicity study was conducted in Sprague Dawley rats at doses up to 31 mg/kg/day, followed by a 14-day recovery period to assess the reversibility of potential toxic effects. Pharmacokinetic analysis revealed that the SMEDDS formulation significantly optimized AN absorption, achieving a 4.3-fold higher maximum plasma concentration (C_max) and a 1.3-fold increase in total systemic exposure (AUC_0-10) compared to the powder suspension. This enhancement was possibly attributed to the pre-solubilized state of AN within nano-sized droplets, which bypasses dissolution rate-limited absorption. The toxicity study established a no-observed-adverse-effect level of 31 mg/kg/day, with no treatment-related mortality, adverse clinical signs, or histopathological lesions observed in vital organs. The AP-SMEDDS effectively overcame the bioavailability constraints of traditional AP extracts while maintaining a promising safety profile. These findings provided robust preclinical evidence to support the clinical translation of this phytopharmaceutical formulation.