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 thelower 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 andspray drying techniques. All formulations were evaluated for delivery efficiency and stability.Susceptibility tests of Mycobacterium species to the drug formulations were carried out. Isoniazidmixed 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 stronglyaffects 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 over3 months storage. These formulations showed that their mass median aerodynamic diameter variedfrom 3.14 ± 0.38 to 4.40 ± 0.65 μm. Drug susceptibility testing of M. tuberculosis by brothmicrodilution showed that the MIC of isoniazid dry powder formulations were 1.7 to 3.4 timeslower 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)