Development of Dry Powder Inhaler Containing Prothionamide-PLGA Nanoparticles Optimized Through Statistical Design: In-vivo Study

Sujit K. Debnath1, *, Saisivam Srinivasan2, Monalisha Debnath1
1 P. G. Institute of Medical Sciences, Chandrakona Town, West Bengal-721201, India
2 N. R. Vekaria Institute of Pharmacy, Junagadh, Gujarat-362001, India

© 2017 Debnath et al.

open-access license: This is an open access article distributed under the terms of the Creative Commons Attribution 4.0 International Public License (CC-BY 4.0), a copy of which is available at: This license permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

* Address correspondence to this author at the P. G. Institute of Medical Sciences, Chandrakona Town, West Bengal-721201, India; Tel: +91-9033924827; Fax: 0343-2534972; E-mail:



The objective of the present work was to formulate Prothionamide (PTH) nanoparticles using Poly lactic co-glycolic acid (PLGA), optimized by Box-Behnken Design and further modification to dry powder inhaler followed by in-vivo study.


Poly-lactic co-gycolic acid (PLGA), a biodegradable polymer was used to coat Prothionamide by solvent evaporation technique. Formulation was optimized using Box-Behnken Design. Response surface curve and desirability factors helped in the selection of optimum formulation of PTH nanoparticles. Dry powder inhaler was prepared by adding inhalable grade lactose to optimize PTH nanoparticles. Mass median aerodynamic diameter (MMAD) was carried out using Andersen Cascade Impactor (ACI) to demonstrate its suitability in the pulmonary administration. In-vitro drug release of dry powder inhaler was carried out in simulated lungs fluid. Correlation in-vitro to in-vivo was established after performing animal experiment.


FTIR study reveals no chemical interaction between PTH, lactose and PLGA as the principle peaks was retained with same intensity in the physical mixture. Scanning electron microscope showed the spherical shape and aerodynamic particle size was found to be 1.69µm. Drug release study showed initial burst release followed by zero order release. In-vivo model confirmed the presence of PTH after 24h. Aerodynamic particle size and the release profile revealed the suitability of PTH loaded nanoparticles containing dry powder inhaler for the pulmonary administration.


Prepared DPI containing PTH nanoparticles can improve in the management of tuberculosis by increasing PTH residency in the lungs tissue for prolong period of time.

Keywords: Tuberculosis, Prothionamide, Dry powder inhaler, Pulmonary administration, PLGA, Box-Behnken design, in-vivo study.