Understanding the In Vivo Impact of Carrier-Drug Inter-Particle Forces Via Engineered Surface Modifications: An In Silico Investigation

A. Mercuri, S. Wu, S. Zellnitz, S. Salar-Behzadi, M. Bresciani, J. Khinast, E. Fröhlich

Engineered modifications of carrier surfaces are used to control the inter-particle forces occurring between the carrier and the drug. In this way, tailoring of these forces enables the quantity of drug that can be delivered to the lungs to be modulated. In this work the impact of engineered modification of carrier-drug surface forces was investigated using glass beads as model carrier particles. Untreated and treated glass beads mixed with salbutamol sulphate were characterised in vitro for their aerodynamic performance. The fine particle fraction (FPF) for treated beads was 1.36 times higher than that for untreated beads. In vivo pharmacokinetic prediction of the surface modifications was investigated after using a validated in silico pharmacokinetic (PK) model. The simulation showed that Cmax for salbutamol released from surface engineered beads was 1.20 fold that of untreated beads. Both in vitro and in silico data showed that increasing the surface roughness of the carrier increased the fine particle delivery performance of the formulation.

Join today to view and download the full abstract/presentation