Impact of the blending process of carrier-based formulations on DPI performance
Inês Fernandes1, Inês Viola2, Luís Sousa3, Ruben Chaves3 & Luís Marques4
1Instituto Superior Técnico, DEQ, Lisboa, 1049-001, Portugal
2NOVA School of Science and Technology, DQ, Caparica, 2829-516, Portugal
3Analytical Development, R&D, Hovione FarmaCiência SA, Lumiar, 1649-038, Portugal
4Inhalation and Advanced Drug Delivery, R&D, Hovione FarmaCiência SA, Lumiar, 1649-038, Portugal
Summary
The pulmonary route has been highly explored for drugs administration due to the advantageous features of lungs. DPI systems encompass a thorough mixing process, where the blending settings influence the resulting formulation characteristics. Carrier-based formulations are widespread solutions for delivery of active ingredients to the lungs in the form of powder. Nevertheless, understanding the cohesive-adhesive balances remains a challenge for pulmonary therapy. To further study this balance, eleven formulations were prepared through different order of addition of the components and different blending energies, to evaluate the impact of these factors on product performance. Statistically, there is no model that could present a viable explanation for the variations observed. However, results demonstrated that greater blending energy improved uniformity and homogeneity. It was recognized that the mixture of an appropriate amount of an excipient’s pre-blend with the API did not impact significantly, in order to establish an accurate correlation. The average content of API in each formulation from BUA analysis was demonstrated to be higher in trials with also a greater Fine particle fraction. DSC data was also obtained for these blends and allowed establishing a correlation between the amount of carrier fines and the drug delivery of the formulation. Therefore, and in agreement with the experimental results, a blending energy of 0.09 mJ/carrier (mixing time of X + 10 min) and the initial addition of the largest portion of pre-blend of excipients to the API (Condition A) revealed to be optimal conditions to obtain a desirable uniformity and enhanced DPI performance.