Spray-dried particles as pulmonary delivery system of anti-tubercular drugs: design, optimization, in vitro and in vivo evaluation

Abstract

Currently, one-third of the world’s population is infected with tuberculosis (TB) mainly spread by inhalation of the tubercle bacilli, Mycobacterium tuberculosis. Patient non-compliance is the major reason for failure of anti-tubercular drugs (ATDs) chemotherapy due to multidrug administration for longer duration of time period. The main aim of current research study was to develop and characterize inhalable spray-dried particles for pulmonary delivery of ATDs, i.e., rifampicin (RIF) and isoniazid (INH). ATDs-loaded alginate particles were prepared by ionotropic gelation technique followed by spray drying and characterized on the basis of various evaluation parameters. Results showed that the optimized spray-dried particles were found to be spherical in shape with excellent flow properties. The drug release showed the biphasic pattern of release, i.e., initial burst (30–40% up to 4 h) followed by a sustained release pattern (90% up to 60 h). Optimized formulations exhibited lower cytotoxicity and excellent lung uptake up to 8 h. Optimized formulation also showed higher rate and extent of drug uptake by lungs due to preferential phagocytosis be macrophage. In future, alginate particles could be a promising carrier for targeted delivery of ATDs to alveolar macrophages for efficient management of TB.

• Alginate
• in vitro and in vivo studies
• pulmonary drug delivery
• spray-dried particle
• tuberculosis

Acknowledgements

The author Mr. Tarun Garg is thankful to the Punjab Technical University (PTU), Kapurthala, Punjab, for providing an opportunity to carry out the research work. Authors also thankful to Indian Council of Medical Research (ICMR), New Delhi, India (AMR/43/2011-ECD-1 dated July 01 2013).

Declaration of interest

The authors report that they have no conflicts of interest. The authors alone are responsible for the content and writing of the paper.