Abstracts from The Aerosol Society Drug Delivery to the Lungs 30 Edinburgh International Conference Centre Edinburgh, Scotland, UK December 11–13, 2019

Abstract

The aim of this study was to improve the storage stability by optimizing the L-leucine coating of our previously described isoniazid formulation for pulmonary administration with the TwincerÒ or CyclopsÒ DPI. Time-of-Flight secondary ion mass spectrometry (TOF-SIMS) showed that trileucine results in higher leucine: isoniazid ratios of 29 and 38 at the surface of the particles, compared to the previously described L-leucine formulation, which has surface ratios of 11 and 28. The trileucine coating improves the stability considerably. All L-leucine formulations are stable for less than a day with the exception for the 3% and 5% formulations spray dried at 120°C and stored at 0% relative humidity (RH), which are stable for at least a month. The trileucine formulations are stable longer. The optimum formulation contains 3% trileucine and is spray dried at 40°C. It is stable for at least three months, even when exposed to 75% RH. This formulation is best dispersed with the CyclopsÒ. While the TwincerÒ results in a higher fine particle fraction (FPF), retention is considerably higher. As a result, the CyclopsÒ results in a higher fine particle dose. The CyclopsÒ can disperse 100 mg, which results in a fine particle dose of 61.9 -1.8 mg. However, 100 mg was the maximum that fit in the inhaler. Further research is needed to study whether a higher dose can be dispersed by increasing the size of the dose compartment, and if this increases the fine particle dose further.