The development of a sensitive methodology to characterise hard shell capsule puncture by dry powder inhaler pins

Abstract

In order for hard-shell capsules to function effectively as drug reservoirs in dry powder inhalers, the capsule must be punctured with sharpened pins to release the powdered medicament upon inspiration. Capsule performance in this setting is poorly understood. This study aims to develop a methodology to characterise hard shell capsule penetration by needles from commercial dry powder inhalers, to determine whether changes to capsule materials impact on their performance. Two pin types from two commercial dry powder inhalers were mounted in a material-testing machine, equipped with a 500 N load cell. A stainless steel bush was used to secure a capsule directly below the steel pin. Hypromellose (n=10) and gelatin capsules (n=10) were conditioned in 'normal' or low humidity conditions and were subsequently punctured with both types of pin. Each puncture event was recorded on a load-displacement curve. The force required for puncture was 2.82±0.26 N for hypromellose capsules and 4.54±0.26 N for gelatin capsules, stored in normal humidity. Different capsule materials possessed distinguishable signature profiles but repeated force-displacement profiles were highly reproducible i.e. intra-individual variability was minimal. A rapid, robust yet sensitive methodology has therefore been developed that is able to characterise hard shell capsule materials based on the puncture performance.

Keywords: Capsule; Dry powder inhaler; Gelatin; Hypromellose; Puncture.