Summary

In this work, four capsule shell formulations (HPMC + gelling agent, HPMC + gelling agent + plasticizer, HPMC without gelling agent, and Gelatin) were filled with salbutamol dry powder inhalation (200 mcg) and lactose carrier.  An accelerated stability program was performed to compare certain efficacy and aerodynamic parameters important for inhalation delivery. 

The filled capsules were analyzed upon puncturing by a single pin dry powder inhalation device at the initial state and then after exposure to 40°C and 75% RH at 1 month, 2 month, 3 month and 6 month intervals.  The seven parameters under evaluation were: assay, fine particle fraction (FPF), drug retention, powder retention, single maximum impurity, total impurities and loss on drying (LOD).

The data yielded valuable results indicating there are differences in performance of certain parameters depending on the specific capsule formulation.  The HPMC capsules + gelling agent + plasticizer performed the best in the accelerated stability study, while the Gelatin capsule performance was the poorest in FPF and drug retention.  These results indicate product development scientists must make an astute selection of capsule types when developing salbutamol. 

Besides the raw material composition used to manufacture the capsule shells and the powder contained within them, the moisture content of the empty capsule shells can influence key testing results.  The water available in the shells can be absorbed by moisture sensitive fills, which can directly impact the puncturing from the device and other measurable parameters from this study.  

Key Message

Different compositions of capsule shells influence various parameters of efficacy and aerodynamic performance of Salbutamol Sulfate formulation.  The capsule selection process for capsule-based inhalation formulations is a key component of the development cycle.  This work highlights capsules shells are not a commodity, but a vital part of drug delivery.