Formulating isoniazid for dry powder inhalation by spray drying

Formulating isoniazid for dry powder inhalation by spray drying

  1. 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 develop an isoniazid dry powder formulation by spray drying with no or a limited amount of excipients. Spray dried isoniazid results in particles too big for pulmonary administration. By adding 1% to 5% of L-leucine a particle size distribution suitable for inhalation was obtained. Storage at an elevated relative humidity of 90% caused the fraction ≤ 5 µm to drop from 92% to 52%. SEM imaging showed that spray drying isoniazid results in large particles consisting of smaller particles fused together, whereas by the addition of L-leucine spherical particles are formed. This morphology is lost after 48h during storage at an elevated relative humidity. The particles become rod shaped and fuse together. X-ray analysis showed that the crystalline structure stays identical and that no different polymorph formed. Spray dried samples show a higher water uptake during DVS analysis in the first cycle compared to the second. This is likely the result of a decrease in surface area when particles fuse together. The fact that the weight does not return to zero after the desorption phase shows that water is taken up permanently. The mechanism by which particles fuse together is unclear. Further experiments have to show whether isoniazid spray dried with L-leucine and stored at lower relative humidity is stable over time and whether the amount of L-leucine can be lowered. Once a stable formulation is obtained dispersion experiments with a dry powder inhaler, such as the Twincer or Cyclops, will be performed.

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