An Original Investigation of the Biopharmaceutical and Pharmacokinetic Properties of Nigerian Herbal Formulations for Malaria Management

Nigerian herbal formulations for malaria management are widely used but their biopharmaceutical properties, including active phytochemical absorption, distribution, metabolism, and elimination (ADME), are largely uncharacterised, limiting scientific understanding of their efficacy, safety, and drug interaction potential. This study conducted an original biopharmaceutical and pharmacokinetic investigation of five widely used Nigerian herbal antimalarial formulations. A comprehensive in vitro and in vivo characterisation methodology was employed. In vitro studies characterised solubility, membrane permeability (Caco-2 cell assay), metabolic stability (liver microsomal assay), and CYP450 inhibition potential of standardised herbal extracts from each formulation. In vivo pharmacokinetic studies in 40 human volunteers from Benue and Kogi States determined plasma concentration-time profiles of key bioactive phytochemicals (artemisinin analogues, quinine alkaloids) by HPLC-MS/MS. Population pharmacokinetic modelling quantified absorption rate constants, bioavailability, and clearance parameters. Results revealed highly variable bioavailability across formulations (range 12 to 68 percent), with low and pH-dependent aqueous solubility as the primary absorption determinant. One formulation demonstrated significant CYP3A4 inhibition (IC50 8.2 micromolar), suggesting drug interaction potential with conventional antiretrovirals and antimalarials. Bioavailability-enhancing formulation strategies (nanoparticle encapsulation and lipid-based drug delivery) were evaluated for the poorest-performing extract, achieving a 3.1-fold bioavailability improvement. This study constitutes an original biopharmaceutics-pharmacokinetics contribution to the scientific characterisation of Nigerian herbal antimalarials.

Keywords: herbal formulations, malaria, biopharmaceutics, pharmacokinetics, Nigerian herbal medicine