(276b) Effect of Carrier Morphology On Drug Loading and in Vitro Aerosolization and Deposition Properties in Dry Powder Inhalation

For dry powder inhalation, large carrier particles are normally mixed with smaller sized active ingredients (API) to improve their inhalation properties. The large carrier particles would experience lower interaction force and can be dispersed from the inhaler easily. As the particle mixture is inhaled, drug particles would detach from the carriers in the initial lung airways and travel further to the lower airways. Therefore, the physical and geometrical properties of the carrier particles are important for efficient drug delivery.

Lactose (LA) particles are commonly used as carriers in dry power formulations. They are of rocklike shape and have limited drug loading capacity. In this study, biocompatible and biodegradable hydroxyapatite (HA) particles with pollen-like surface are proposed as drug carriers. The pollen-like surface provides high drug loading capabilities. The depositions of drugs are studied in vitro and the performance of HA carriers are compared against LA carriers. Budesonide (Bd) is chosen as the model drug and it is blended with different carriers with carrier to drug weight ratio of 2:1, 10:1 and 45:1. Formulations with HA carriers show good blending homogeneity and stability. The characterization of the formulations shows that HA carriers are capable of higher drug loading than LA carriers. A large amount of the Bd particles are found unattached in the formulations with LA carriers. In the in vitro deposition study, experiments are conducted at 30 and 60 liter/min via Rotahaler® using an Anderson Cascade impactor (ACI). Formulations of HA and LA carriers with different drug loadings are tested. At a flow rate of 30 liter/min, the unattached Bd particles from LA carriers are found to coagulate with each other and stick to the surface of the container and inhaler. The emitted dose (ED) and fine particle fraction (FPF) of Bd using HA carriers are higher than that using LA carriers with all blending ratios. As the flow rate is increased to 60 liter/min, even though the ED and FPF of Bd using HA carriers are still higher than that using LA carriers, the difference between the two carriers are less significant. The findings of this study confirm that the delivery efficiency of inhaled therapeutics can be improved by introducing a unique pollen-like morphology of carrier particles which would reduce the drug loss at higher drug loading and improve the aerosolization and deposition properties significantly.