Summary
Dry powder inhaler (DPI) functionality and efficiency is governed by the complex surface interaction between the micronized active pharmaceutical ingredient (API) and the excipient particles. It is known that blends manufactured by high energy mixing processes can change overtime due to material relaxation, however no data are publicly available for fluticasone furoate (FF). Therefore, throughout the development of a Relvar® Ellipta generic, we monitored the interaction between blend composition and the relaxation effect of FF blends upon ambient storage. A relaxation effect with a statistically significant increase of respirability was noticed for the blends comprising the finer grade of fine lactose. This was greater when a lower percentage of fine lactose was used, but generally it resulted in a higher deposition in stages 3 and 4 of the NGI for all the stability time-points compared to time zero. The same relaxation effect was not observed for the other FF blends manufactured with the same API or a coarser batch with slightly lower amorphous content and a different grade of lactose fine. On the contrary to what reported for fluticasone propionate where relaxation of the amorphous disorder influenced adhesive-cohesive balance, the same correlation was not observed for FF in this small dataset. Further studies will be necessary to correlate API and excipients’ physico-chemical properties and high shear mixing parameters to the relaxation effect observed. However, when developing a DPI by high shear blending, it should be good practice to monitor and control drug product variability upon storage since initial formulation screening.