Enhancing bedaquiline solubility with advanced approaches for optimized tubercular therapy

The global resurgence of Mycobacterium tuberculosis strains exhibiting Extensive and Multidrug resistant tuberculosis (XDR and MDR-TB) is posing a strong challenge and burden on healthcare sector worldwide. The conventional first line and second line treatment options often showed unsatisfactory clinical outcomes. To overcome the challenges associated-with TB a new drug bedaquiline (BDQ) has emerged as a promising therapeutic advancement. BDQ is a diarylquinoline compound that can inhibit bacteria through targeting mycobacterial ATP synthase, resulting in improved therapeutic efficacy against resistant mycobacterial strains managing XDR/MDR TB. However, its therapeutic efficacy is compromised due to its extremely poor aqueous solubility and low dissolution rate limited bioavailability, compelling the necessity for advanced formulation strategies. The review aimed at summarizing the newer strategies to improve the solubility of BDQ, through various approaches including solid dispersion, microemulsion, solid lipid nanoparticles, polymeric micelles etc. The outcome of each approach has been discussed which compiles the suitability of applied solubility enhancement strategy. Among all the techniques covered to best of our knowledge solid dispersions and SNEDDS demonstrated the most practical translational potential, while lipid-based and nano-enabled systems offer opportunities for targeted delivery and dose reduction. This review aims to bridge laboratory advancements with industrial feasibility, assisting pharmaceutical developers in selecting robust, scalable, and regulatory-friendly strategies for improving BDQ delivery.