Abstract

Dry powder inhalers (DPIs) are known to be sensitive to humidity. Erroneous storage of these products by patients in high humidity environments, could present a potential risk. Therefore, an in-vitro-in-silico approach was utilized to assess the risk that patient erroneous storage might pose. For this two commercial DPIs containing lactose and budesonide (Easyhaler® and Novolizer®) were used. These were evaluated in respect to their physical solid-state and micrometric properties as well as their in-vitro aerodynamic performance. Testing was carried out at time 0, 14 and 28 days after storage at 60% RH and > 90% RH. Using in-silico modeling the potential impact of powder sensitivity to humidity on the biopharmaceutical performance of budesonide was evaluated. Results revealed that the physical and aerodynamic properties of the powders having a smaller carrier particle size and a higher amount of excipient fines were more notably affected. Use of in-vitro results as inputs for in-silico pharmacokinetic modeling showed that some changes in powder properties can have a potential impact on the pulmonary availability of budesonide. So, it appears that it is important to consider the impact that different product characteristics might have on the physical stability of powders against moisture and their subsequent biopharmaceutical performance.