IVIVC using in silico and PBPK methods for inhaled drug product development

This study demonstrated the potential of using an IVIVC to evaluate the in vivo dissolution rates for inhaled products. However, a sensitive method for predicting the differences in lung deposition is required for more accurate prediction of overall systemic exposure after inhaled administration. The model showed a good correlation between the fitted total lung deposition and MMAD of the API. Further studies are needed to evaluate the applicability domain of such correlations and possible other manufacturing aspects that might affect the lung deposition of the API. The PBPK models developed using Cp-time profiles from literature were able to describe the PK of each API after inhaled administration of the reference formulation from the current clinical study with only the expected changes in the lung deposition and dissolution rates. Despite similar particle sizes of the two APIs (as measured in cascade impactor), API2 required 40% higher total lung deposition to accurately match the observed exposure after inhalation of the reference formulation (Table 1).