Investigation of the Equilibrium Relative Humidity of Commercial Capsule Based Dry Powder Inhaler Products

Authors: , , ,

Hermetically sealing capsule-based dry powder inhaler (DPI) systems at a low relative humidity has numerous benefits such as increased shelf-life, sustained released-dose reproducibility, and a retained expected product performance. Moisture entrapped in hard capsule shells can transfer to the formulation causing an imbalance in the equilibrium conditions achieved under initial packaging giving physicochemical stability issues. If moisture was to egress from the capsule, it would migrate into the powder contained in the capsule and not into the surrounding cavity headspace. Amorphous powders packaged and held under a specific humidity will retain their desired glass transition temperature and hence remain stable over its shelf-life. Equilibration of individual components at a humidity dependant on the characteristics of the powder must occur for a stable marketable product.
Investigations into the headspace humidity of the blistering cavity for several commercial products were carried out to determine packaging, transport and storage requirements for a stable capsule-based DPI. The effect of gelatin capsules on the characteristics of a formulation under different humidities and an elevated temperature of 40°C is shown. A formulation named University of Bath (UoB) was prepared and filled into a gelatin capsule. After accelerated stability conditions of 40°C / 75%RH, its initial packaging humidity of 30% RH was retained. This suggests that the effect of external environmental conditions are minimised if components are brought together under a common equilibrium state and packaged under these conditions.