Coconut Oil-based SNEDDS Loaded with Rifampicin Improves Oral Bioavailability and Drug Safety

Rifampicin (RIF) is a first-line antitubercular (anti-Tb) drug despite its decreased oral bioavailability and remarkable hepatotoxicity owing to its poor aqueous solubility. A coconut oil-based RIF-loaded self-nanoemulsifying drug delivery system (RF1) was developed beforehand to resolve the solubility issue. This work aimed to appraise the pharmacokinetic (PK) profiles and safety properties of RF1 for future endeavors. The comparative PK and safety profiles of pure RIF and the RF1 formulation were elucidated after oral administration to Wistar rats. In the PK study, blood sample was collected at definite time intervals from experimentally grouped animals orally administered raw RIF or RF1 at dose of 50 mg/kg body weight (b.w.). For the safety study, pure RIF and formulated RF1 were administered consecutively for fourteen days, dosed 50 and 125 mg/kg b.w. Twenty-four hours after final dose, the blood, liver, and kidney samples were amassed for biochemical analysis and histological characterization. RF1 revealed a 1.5-fold greater relative bioavailability (F) and a 1.4-fold greater Cmax within 30 min (Tmax) than did raw RIF, resulting in an improved AUC0-480 of RF1, with a comparable mean residence time and elimination half-life of the drug, indicating its potential pharmacological efficacy. Moreover, the in vivo safety evaluation revealed RF1 as innocuous as pure RIF, as characterized by liver and kidney markers and corresponding histological observations. Based on the findings from PK and safety studies, the SNEDDS of RIF might be a potential alternative for delivering rifampicin orally and may improve bioavailability while minimizing toxicity.