Assistance for Predicting Deposition of Tranilast Dry Powder in Pulmonary Airways by Computational Fluid Dynamics

Abstract

Computational fluid dynamics (CFD) simulation was performed to predict deposition behavior of the dry powder inhaler (DPI) formulation in a pulmonary airway model. A synergistic study on CFD simulation and sample preparation with highly branched cyclic dextrin (HBCD) as an excipient matrix for dry powder inhaler formulations of tranilast (TL) were performed. The crystal form of TL in spray-dried particles was characterized by powder X-ray diffraction and fluorescence spectroscopy. The aerodynamic performance of DPI formulations was assessed using the Andersen cascade impactor. CFD simulations could simulate the movement of fluids by resolving the mathematic equations governing the movement following Navier-Stokes equations. Particle behavior and deposition from CFD analysis compared with experimental data. Spray-dried particles (SDPs) of TL/HBCD showed characteristic diffraction peaks differing from untreated TL crystalline in powder X-ray diffraction. The polymorphic transition of TL was also observed in a fluorescence spectrum. Cascade impactor evaluation on SDPs of TL/HBCD at a 40% ethanol ratio demonstrated high inhalation performance with a fine particle fraction of 33%, while SDPs prepared at a 30% ethanol ratio were lower than that of the others. Regarding the cause of this difference, CFD analysis revealed that high inhalation performance was related to the true density and particle size of SDPs. The change in true density of TL associated with polymorphic transition would affect the inhalation performance. The results on CFD simulations made a prediction about the particle behavior or deposition in pulmonary airways.