Formulating amikacin for dry powder inhalation

Imco Sibum

Formulating amikacin for dry powder inhalation

I. Sibum, F. Grasmeijer, P. Hagedoorn & H.W. Frijlink

 Department of Pharmaceutical Technology and Biopharmacy, Ant. Deusinglaan 1, Groningen, 9713 AV, the Netherlands


The aim of this study was to formulate amikacin as a dry powder inhalation product by spray drying with the least amount of excipients possible. Pure spray dried amikacin results in a primary particle size distribution suitable for pulmonary administration. However, due to the co- and adhesiveness of the powder, dispersion from our Cyclops® inhaler was poor. By adding 1 or 2% L-leucine dispersion was improved significantly without affecting the primary particle size distribution. Inhaler retention dropped from 50% to around 8% while the fine particle fraction improved from approximately 11% to 50%. This is likely a result of the fact that L-leucine has the tendency to form a coating around powder particles during spray drying. L-leucine is less co- and adhesive than amikacin and as a result dispersion is improved. As there was no significant difference between the 1 and 2% L-leucine samples the stability study was performed on the 1% L-leucine formulation. This stability study showed that the fine particle fraction stayed stable during 6 months under long-term and accelerated storage conditions. Inhaler retention was between 10.92 ± 2.75% and 22.48 ± 8.27% but no trend in time could be discerned. A pharmacokinetic evaluation and local tolerability clinical study is currently in preparation to study the suitability of this formulation for the treatment of tuberculosis patients.

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