US EPA

6575323 

Journal Article 

Characterization and Formulation of Isoniazid for High-Dose Dry Powder Inhalation 

Sibum, I; Hagedoorn, P; Frijlink, HW; Grasmeijer, F; , 

2019 

1 

Pharmaceutics
EISSN: 1999-4923 

MDPI 

BASEL 

11 

5 

English 

31086107 

10.3390/pharmaceutics11050233 

WOS:000470962600038 

Tuberculosis is a major health problem and remains one of the main causes of mortality. In recent years, there has been an increased interest in the pulmonary delivery of antibiotics to treat tuberculosis. Isoniazid is one of these antibiotics. In this study, we aimed to characterize isoniazid and formulate it into a dry powder for pulmonary administration with little or no excipient, and for use in the disposable Twincer((R)) inhaler. Isoniazid was jet milled and spray dried with and without the excipient l-leucine. Physiochemical characterization showed that isoniazid has a low Tg of -3.99 +/- 0.18 degrees C and starts to sublimate around 80 degrees C. Milling isoniazid with and without excipients did not result in a suitable formulation, as it resulted in a low and highly variable fine particle fraction. Spray drying pure isoniazid resulted in particles too large for pulmonary administration. The addition of 5% l-leucine resulted in a fraction <5 mu m = 89.61% +/- 1.77% from spray drying, which dispersed well from the Twincer((R)). However, storage stability was poor at higher relative humidity, which likely results from dissolution-crystallization. Therefore, follow up research is needed to further optimize this spray dried formulation.