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.

Dry powder inhalers (DPIs) are favorable devices for the delivery of dry formulations to the lungs; still, they largely fail to deliver higher doses of active pharmaceutical ingredient (API) to the lower airways. Addition of fine particles of excipient (fines) to the blend of API and carrier was shown to improve aerosolization performance. Lactose monohydrate is ubiquitous excipient used for this purpose. Lactose exists in a thermodynamically stable crystalline form; however, processes like milling, sieving, or even mixing may induce alteration of crystalline structure and introduce amorphous domains, which could further affect the physico-chemical properties of the material. Therefore, the aim of this work is a detailed characterization of two commercially available types of inhalation grade fine lactose powders (Inhalac 400 and Inhalac 500) prepared using different air-jet milling parameters, with a focus on impact of storage conditions on material properties. We found that the different milling parameters resulted in variable particle size distribution (PSD), and thus surface areas, variable initial amorphous content, cohesivity, flowability, and moisture sorption of materials. In addition, exposure of fine powders to higher humidity reduced the amorphous content present in the materials, but also affected agglomeration tendency and dispersion behavior of both powders. We believe the obtained findings to be important for the aerosolization performance of carrier-based DPIs containing fines and thus need to be duly considered during formulation development.

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