Background/Objectives: This study investigates the impact of high humidity (25 °C,
75% relative humidity) on gelatin and hydroxypropyl methylcellulose (HPMC) capsules
used in dry powder inhalers (DPIs), focusing on moisture dynamics, structural responses,
and mechanical performance, with an emphasis on understanding how different capsule
types respond to prolonged exposure to humid conditions. Methods: Capsules were exposed
to controlled humidity conditions, and moisture uptake was measured via thermal analysis.
Visual observations of silica bead color changes were performed to assess moisture
absorption, while surface wettability was measured using the sessile drop method.
Hardness testing, mechanical deformation, and puncture tests were performed to evaluate
structural and mechanical changes. Positron annihilation lifetime spectroscopy (PALS)
was used to analyze free volume expansion. Results: HPMC capsules exhibited rapid
moisture uptake, attributed to their lower equilibrium moisture content and ability
to rearrange dynamically, preventing brittleness. In contrast, gelatin capsules showed
slower moisture absorption but reached higher equilibrium levels, resulting in plasticization
and softening. Mechanical testing showed that HPMC capsules retained structural integrity
with minimal deformation, while gelatin capsules became softer and exhibited reduced
puncture resistance. Structural analysis revealed greater free volume expansion in
HPMC capsules, consistent with their amorphous nature, compared with gelatin’s semi-crystalline
matrix. Conclusions: HPMC capsules demonstrated superior humidity resilience, making
them more suitable for protecting moisture-sensitive active pharmaceutical ingredients
(APIs) in DPI formulations. These findings underline the importance of appropriate
storage conditions, as outlined in the Summary of Product Characteristics, to ensure
optimal capsule performance throughout patient use.
