No abstract

Capsule-based dry powder inhaler (DPI) products can be influenced by a multitude of interacting factors, including electrostatic charging. Tribo-charging is a process of charge transfer impacted by various factors, i.e., material surface characteristics, mechanical properties, processing parameters and environmental conditions. Consequently, this work aimed to assess how the charging behavior of capsules intended for inhalation might be influenced by environmental conditions. Capsules having different chemical compositions (gelatin and hydroxypropyl methylcellulose (HPMC)) and distinct inherent characteristics from manufacturing (thermally and cold-gelled) were exposed to various environmental conditions (11%, 22% and 51% RH). Their resulting properties were characterized and tribo-charging behavior was measured against stainless steel and PVC. It was observed that all capsule materials tended to charge to a higher extent when in contact with PVC. The tribo-charging of the thermally gelled HPMC capsules (Vcaps ® Plus) was more similar to the gelatin capsules (Quali-G™-I) than to their HPMC cold-gelled counterparts (Quali-V ®-I). The sorption of water by the capsules at different relative humidities notably impacted their properties and tribo-charging behavior. Different interactions between the tested materials and water molecules were identified and are proposed to be the driver of distinct charging behaviors. Finally, we showed that depending on the capsule types, distinct environmental conditions are necessary to mitigate charging and assure optimal behavior of the capsules.

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.