Quality by design approach for development and optimization of rifampicin loaded nanoparticles and characterization

Background: Rifampicin is an effective in the treatment of sensitive, non-resistant strains of mycobacterium tuberculosis. Thus there is need to develop a rifampicin loaded nanoparticles.
Aim: This study is focused on development of RFM loaded nanoparticles, characterization to achieve lung targeting using quality by design approach.
Objectives: The main objective of this study is optimizing particle size and entrapment efficiency of rifampicin-loaded nanoparticles and making them suitable for nebulizer application using QbD approach.
Methods: Quality target product profile was defined along with critical quality attributes for the formulation. Preparation of nanoparticle dry powder inhaler formulation were numerous methods such as microemulsion solvent  evaporation,  ionic gelation and  modified ionic gelation followed by probe sonication were employed for the preparation of nanoparticles and  the  final  method  of  preparation  was  selected  based  on  particle  size,  zeta  potential, entrapment efficiency and drug loading.
Results: The optimized RFM-loaded nanoparticles were characterized by UV spectroscopy, FTIR, DSC techniques. The observed nanoparticles were spherical in shape. The TPP concentration, stirring speed and concentration of acetic acid were playing a crucial role in the successful formation of nanoparticles and were selected for optimization. In vitro release study showed 100% release of pure RFM within 12 hrs and the optimized chitosan nanoparticle formulation loaded with RFM showed nearly 90% release of RFM within 24 hr.
Conclusion: Rifampicin loaded nanoparticle DPI formulations achieve lung targeting and the delivery of drug into the lungs will also prevent the first pass metabolism, thus, leading to reduction in the dose of the drug as well as related side effects. These drug targeting approaches may serve as a boon in the effective treatment of tuberculosis.