Research Article: Evaluation of the Physico-mechanical Properties and Electrostatic Charging Behavior of Different Capsule Types for Inhalation Under Distinct Environmental Conditions

Date Published: May 12, 2020

Publisher: Springer International Publishing

Author(s): Joana T. Pinto, Thomas Wutscher, Milica Stankovic-Brandl, Sarah Zellnitz, Stefano Biserni, Alberto Mercandelli, Mirjam Kobler, Francesca Buttini, Laura Andrade, Veronica Daza, Susana Ecenarro, Laura Canalejas, Amrit Paudel.

http://doi.org/10.1208/s12249-020-01676-2

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.

Partial Text

Dry powder inhalers (DPIs) deliver powder formulations containing active pharmaceutical ingredients (APIs) to the lungs through patients’ inhalation. They are mainly used in the treatment of respiratory diseases such as asthma, chronic obstructive pulmonary disease (COPD), and cystic fibrosis (36). The powder formulation is delivered using a device that allows its aerosolization and adequate delivery to the lung (15). DPI devices vary widely in design (7). Depending on whether the inhalers are breath-activated or not, these can be further categorized as passive or active devices, respectively (8). DPI devices contain either single or multi-doses. Multi-dose inhalers contain the powder stored as a bulk in a reservoir within the device to be metered prior to actuation, or alternatively, the powder is contained inside a series of pre-metered unit doses (blisters, capsules, tubes, dimples) that are delivered as single doses during each actuation (2,23). In a single dose inhaler, the patient has to load a pre-metered single dose of the powder into the device before each use (23). Pre-meter dosing is most commonly carried out using capsules (2,11,23).

Tribo-charging can have a detrimental impact on the handling of pharmaceutical materials and can affect the aerodynamic performance and thus the pulmonary delivery of the API. In this study, the tribo-charging of capsules intended for dry powder inhalation was related to their inherent chemical composition, manufacturing process, and environmental humidity. We have shown that HPMC capsules manufactured using two different processes (thermally and cold-gelled) result in distinct tribo-charging behaviors. The Vcaps® Plus capsules charged more after storage at lower humidities; in turn, Quali-V®-I samples were found to charge to a higher extent after conditioning at higher RHs. All capsules tended to charge to a higher extent in contact with PVC. The thermally gelled HPMC capsules charged more similarly to Quali-G™-I samples than to their HPMC Quali-V®-I counterparts. The sorption of water by the capsules notably impacted their mechanical properties and tribo-charging behavior. Different interactions between the polymers and water molecules were proposed to be the source of dissimilar tribo-charging behaviors, further evidencing the complex role of water in the tribo-charging of insulator materials. Finally, we showed that distinct environmental conditions might be necessary to control tribo-charging and ensure the optimal behavior (for e.g., during processability) of different pharmaceutical capsule materials.

 

Source:

http://doi.org/10.1208/s12249-020-01676-2

 

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