Impact of Capsule Size and Device Resistance on required Flow Rate to evaluate Dry Powder Inhalers

CALDAROLA, MARÍA PAULA; CESCHAN, NAZARETH ELIANA; CABRERA, FERNANDA; RAMIREZ RIGO, MARÍA VERÓNICA

Rosario

Congreso; 7ma Edición de la Reunión Internacional de Ciencias Farmacéuticas; 2023

Universidad Nacional de Rosario

Dry Powder Inhalers (DPIs) are the preferred technology for prescribers and patients for the administration of inhaled medications. This is due to their competitive advantages over other inhalatory systems (e.g. nebulizers), in terms of portability, usage times and stability. However, for high dose drugs, like antibiotics and mucolytics used in some obstructive respiratory diseases, the design of DPIs represents a challenge. High number of capsules carrying the formulation are required to achieve a therapeutic dose. Therefore, in recent years there has been an increasing interest in the development of DPIs that maximize dry powder load. Airflow resistance of conventional mono-dose devices using #3 capsules has been previously evaluated [1]. The aim of this work was to study the impact of capsule´s presence and its size in the required flow rate to achieve the compendia specifications during the evaluation of new DPI device designs (DDs). Seven models of single dose, capsule-based RS01 inhalers were studied. According to USP, the inhalers are evaluated at a 4 kPa pressure drop (∆P) across them. Each DPI was evaluated with (IC) and without (INC) #2 and #3 gelatin empty capsules. The flow rate (Q) needed to achieve the target ∆P and the device resistance (R) were determined in vitro using a Critical Flow Controller, attached in-line with a dosage unit sampling apparatus and a vacuum pump. Also, Clark and Hollingsworth's equation was used for R calculations as well. The results revealed that for INC measurements, R values were 0.019 – 0.033 kPa0.5.min.L-1 for devices for #2 capsules and 0.019 - 0.045 kPa0.5.min.L-1 for devices for #3 capsules. This indicates that the required Q for INC ranged between 44.1 ± 0.8 and 106.6 ± 0.9 L/min. Also, in six of seven DPI models (85.7%), IC exhibited an R value that is 5.9 – 10.8% lower than INC. Differences found were statistically significant: (a) for IC and INC, only for devices with higher resistances; (b) across different DD, in all cases. Furthermore, differences in capsule sizes were not statistically significant for low R devices, but for high R devices. These findings suggest that capsule´s presence and its size induce alterations in the airflow patterns within the DPIs when R is kept constant. According to other authors, this may be due to the way the capsule rotates and the geometry of the chamber that contains it [2]. As expected, the DD changes airflow patterns when capsule size and its presence is kept constant. In conclusion, to meet compendia standards Q should be adjusted depending on the DD in order to achieve a comparable aerodynamic performance. Also, presence of capsule and capsule size impact on device R, which in turn can affect DPI performace.