An in vitro and in silico study of the impact of engineered surface modifications on drug detachment from model carriers.

In silico modeling was used to predict the impact of carrier surface modifications on the in vivo plasma concentration of an active pharmaceutical ingredient (API) and as a tool to support formulation development. In vitro fine particle fraction (FPF) and mass median aerodynamic diameter (MMAD) of salbutamol sulphate delivered from Cyclocaps®, detached from unmodified and surface engineered glass beads were measured using a Next Generation Impactor (NGI). Surface roughness was chosen to classify surface modification/engineering and it was evaluated via scanning electron microscopy (SEM) and image analysis. An in silico pharmacokinetic (PK) model was built and the quality confirmed with available literature data. Plasma profiles were generated combining the PK model with in silico deposition models for salbutamol sulphate released from Cyclocaps®, unmodified and surface engineered glass beads. The increased roughness of the surface of engineered beads resulted in a FPF 1.36 times higher than that of untreated beads. Cmax from the in silico plasma profile of salbutamol released from the surface engineered beads was 1.20 fold higher than that from untreated beads. Increasing the surface roughness was found to augment the amount of drug loading and detaching from the carrier both in vitro and in silico.