Evaluating Drug Deposition Patterns from Turbuhaler® in Healthy and Diseased Lung Models of Preschool Children

The efficacy of pediatric oral drug delivery using dry powder inhalers, such as Turbuhaler®, is dependent on the age and health of the test subjects. The available clinical data for these studies is scant and rarely provide correlations between the health condition and the regional lung deposition. In particular, the data and the correlations for pre-school children are minimal. Deposition simulations were performed using the newly developed Quasi-3D whole lung model to analyze the effect of health conditions on the regional lung deposition from the Turbuhaler® in 3-year-old children. The healthy lung model was created from CT scan data. Cystic-fibrosis models were created by uniformly constricting the airways to various degrees. The simulated drug deposition outcomes were validated against the available experimental data. The results show that, while the dose deposited in the lungs exhibits minor variations, the Peripheral:Central (P/C) ratio is strongly affected by both the health condition and the inflow variations. The above ratio is reduced by ~30% for the severely diseased case, compared to its healthy counterpart, for the same inhalation profile. This indicates that lower doses reach the peripheral lung, in pediatric cystic-fibrosis subjects, thus requiring a larger therapeutic dose.