Filling the Void in Pediatric Tuberculosis Treatment: Challenges and the Promise of Rifampicin Self-Emulsifying Drug Delivery Systems

Tuberculosis (TB) persists as a devastating global health crisis, exacting a disproportionate burden on low-middle-income countries (LMIC), within which the burgeoning pediatric TB population is especially vulnerable to severe TB manifestations. Rifampicin, a cornerstone of the first-line TB regimen, is indispensable; yet its therapeutic potential is substantially constrained by intrinsic poor aqueous solubility, limited permeability, physicochemical instabilities, and deleterious drug-drug interactions with drugs such as isoniazid. Although current research focuses on formulating rifampicin into fixed-dose combinations – some reporting improved outcomes – the variable and often suboptimal rifampicin bioavailability in such formulations remains a critical concern. Consequently, the development of a stable, independent rifampicin oral formulation should be prioritized to ensure effective TB treatment. There are currently no commercially available rifampicin-only liquid preparations, despite the urgent need for palatable, flexible, age-appropriate formulations. This paucity constitutes a profound and persistent gap in pediatric TB, compromising accurate weight-based dosing, treatment adherence, and therapeutic outcomes while contributing to rifampicin resistance. This paper highlights the key characteristics and formulation challenges of rifampicin, with particular emphasis on pediatric TB. It further discusses liquid self-emulsifying drug delivery systems (SEDDSs) as a novel approach to enhance oral rifampicin delivery. These feasible lipid-based delivery systems offer notable promise, as they are capable of maintaining rifampicin in a solubilized and stable state throughout the gastrointestinal tract, which in turn will likely improve bioavailability. The possible development of a stable liquid rifampicin SEDDS represents a paradigm shift in addressing the longstanding neglect of pediatric TB treatment.