PREPARATION OF ISONIAZID AS DRY POWDER FORMULATIONS FOR INHALATION BY PHYSICAL MIXING AND SPRAY DRYING

The main purpose of this study is to develop isoniazid as dry powder aerosol for delivery to the lower airways and to study the susceptibility of M. bovis and M. tuberculosis to the formulationsstudied. Isoniazid was formulated with trehalose, mannose and lactose by physical mixing and spray drying techniques. All formulations were evaluated for delivery efficiency and stability.Susceptibility tests of Mycobacterium species to the drug formulations were carried out. Isoniazid mixed with fine trehalose, micronised mannose or fine lactose produced the formulations whichgave fine particle fraction (< 5 μm) of over 60%. The different size of carrier particles strongly affects the deposition of isoniazid to the lower airways in vitro. The content of all isoniazid drypowder formulations was almost 100% of the theoretical content and found to be stable over 3 months storage. These formulations showed that their mass median aerodynamic diameter varied from 3.14 ± 0.38 to 4.40 ± 0.65 μm. Drug susceptibility testing of M. tuberculosis by broth microdilution showed that the MIC of isoniazid dry powder formulations were 1.7 to 3.4 times lower than standard isoniazid. Flow cytometry analysis of viable M. bovis revealed that MIC ofisoniazid dry powder formulations and standard isoniazid had no significant difference (p > 0.05).