Formulation and optimisation of bedaquiline nanoemulsions for the potential treatment of multi drug resistant tuberculosis in paediatrics using quality by design

Abstract

Abstract Bedaquiline is a drug used for the treatment of multidrug-resistant TB in adults and children that is currently only commercially available in tablet form. The present study was aimed at preparing nanoemulsion (NE) of BDQ using natural vegetable oils to deliver BDQ. The optimisation of surfactant mixtures was undertaken using Design of Experiments (DoE), specifically an optimal mixture design. The NEs were optimised while monitoring droplet size (DS), zeta potential (ZP), polydispersity index (PDI) and drug content (DC). The optimised NEs were further characterised using transmission electron microscopy, electrical conductivity, viscosity, pH and in vitro release studies. The optimised NE showed values of 191.6 nm ± 2.38 nm, 0.1176 ± 1.69, -25.9 mV ± 3.00 mV and 3.14 ± 0.82 mg/ml for DS, PDI, ZP and DC respectively. Furthermore, the TEM studies demonstrated the spherical shape of the optimised globules. The nanoemulsion was characterised by measuring its electrical conductivity, viscosity and pH which were determined as 53.1 µS/cm, 327 ± 3.05 cP and 5.63 ± 1.78, respectively. In conclusion, these NEs have great potential for improving solubility, drug delivery, and administration of BDQ. However, further studies are required to maximise the drug content and to demonstrate to what extent these NE have effect against MDR-TB.

Keywords

• Nanoemulsions
• Bedaquiline
• Drug Release
• Droplet size
• Zeta potential
• Quality by Design