Oral Delivery of Tocotrienols: Addressing Pharmacokinetic Challenges With Formulation‐Based Strategies

Tocotrienols (T3), vitamin E analogues with potent antioxidant and therapeutic properties, have attracted increasing scientific interest. However, their clinical translation is hindered by poor and variable oral bioavailability. This limitation arises from their low aqueous solubility, rapid elimination, chemical instability and weak affinity for α-tocopherol transfer protein, which restricts systemic retention and tissue distribution. The intestinal absorption of T3 is a saturable, concentration-dependent process mediated primarily by Niemann-Pick C1-like 1 and, to a lesser extent, scavenger receptor class B type 1. This review outlines the pharmacokinetics of T3 and critically examines recent advances in oral delivery systems aimed at improving bioavailability. While existing approaches offer improvement in bioavailability, intrinsic absorption barriers remain a challenge. Future progress requires integrating both physicochemical and biological strategies, focusing on modulating intestinal transporters and controlling the release kinetics to mitigate local saturation. Such next-generation formulations may enable consistent absorption, prolonged circulation, and enhanced therapeutic efficacy of T3.