Background: During the development of inhalation products, using animal models is inevitable for the evaluation of formulation. To comply with the 3R principle (reduction, refinement, and replacement of animal experiments) and to reduce costs, it is desirable to predict the efficacy of formulations based on theoretical calculations. In the current study we evaluated the suitability of in silico tools to predict the in vivo pharmacokinetic data of inhaled drugs.
Methods: GastroPlus™ with Additional Dosage Routes Module™ was used for the simulation studies. The in vivo data of a metered dose of 1.0 mg budesonide after administration either by a Turbuhaler® or by a pMDI + Nebuhaler® were taken from literature and compared with the simulated data.
Results: Generally, the in silico data were comparable with the in vivo. Simulations with GastroPlusTM predicted higher bioavailability and higher plasma levels of budesonide using Turbuhaler compared to pMDI + Nebuhaler. Absolute data for bioavailability was relatively higher and plasma levels were relatively lower in GastroPlusTM than in vivo data. This apparent discrepancy could be due to the slow excretion rate reported in the literature.
Additionally, the calculation models used for the in silico simulation have a great influence on the obtained bioavailability values.
Conclusion: In this study we have shown the suitability of in silico modeling for supporting pulmonary drug development. Such models offer a useful tool for linking the drug product properties to in vivo performance, enabling the implementation of Quality by Design in inhalation drug development and the reduction of animal experimentation by improved selection of candidates.