In the present investigation inhaled isoniazid microparticles (IM) and isoniazid polymeric microparticles (INH-PM) using poly-epsilon-caprolactone polymer were prepared through spray drying techniques. The purpose of this investigation is to evaluate lung deposition of IM and INH-PM through cascade impaction study. The drug release of IM and INH-PM was studied using simulated lung fluids at pH 7.4 representing the interstitial site and at pH 4.5 representing phagocomal site after alveolar macrophage uptake. The kinetic models had also been applied providing the drug release kinetics for IM and INH-PM in simulated lung fluids at pH 7.4 and at pH 4.5. The results of the particles size and surface characteristics showed the spherical shape and 1-5 mu m size of IM and INH-PM prepared using spray drying which can be suitable for pulmonary drug delivery. The cascade impaction study with mass median aerodynamic diameter ranging from 1.9 to 4 mu m confirmed the inhaled characteristics of IM and INH-PM with providing the deep lung deposition where tubercular bacilli reside. From in vitro drug release studies done using simulated lung fluids and goodness of fit with kinetic model applications, it can be concluded that the prepared poly-e-caprolactone microparticles of isoniazid provided the advantage of controlled release characteristics deep inside the lung where tubercular bacilli reside and as suitable for pulmonary drug delivery it may help in improving treatment of tuberculosis through direct administration to site of action. (C) 2014 Elsevier B.V. All rights reserved.