Retention-time prediction for polycyclic aromatic compounds in reversed-phase capillary electro-chromatography.

Log Po/w based models are often used for the retention time prediction of reversed phase liquid chromatography. Here, we present the investigation of the applicability of log Po/w based retention time predictions for the separation in capillary electro-chromatography (CEC). A test set of five polycyclic aromatic hydrocarbons was separated using two different stationary phases with three different mobile phases each. The resulting retention times were correlated with the experimental log Po/w values as well as with calculated log Po/w values. The used methods include quantitative structure property relationship (QSPR) models as well as molecular dynamic methods such as the linear interaction energy (LIE) or the Bennett acceptance ratio (BAR). The results indicate that rigorous simulation models are capable of accurately reproducing experimental results and that the electrophoretic mobility of analytes in CEC separations leads to significant deviations in the retention time prediction.

Investigation of migrant-polymer interaction in pharmaceutical packaging material using the linear interaction energy algorithm.

The interaction between drug products and polymeric packaging materials is an important topic in the pharmaceutical industry and often associated with high costs because of the required elaborative interaction studies. Therefore, a theoretical prediction of such interactions would be beneficial. Often, material parameters such as the octanol water partition coefficient are used to predict the partitioning of migrant molecules between a solvent and a polymeric packaging material. Here, we present the investigation of the partitioning of various migrant molecules between polymers and solvents using molecular dynamics simulations for the calculation of interaction energies. Our results show that the use of a model for the interaction between the migrant and the polymer at atomistic detail can yield significantly better results when predicting the polymer solvent partitioning than a model based on the octanol water partition coefficient.

Prediction of drug-packaging interactions via molecular dynamics (MD) simulations.

The interaction between packaging materials and drug products is an important issue for the pharmaceutical industry, since during manufacturing, processing and storage a drug product is continuously exposed to various packaging materials. The experimental investigation of a great variety of different packaging material-drug product combinations in terms of efficacy and safety can be a costly and time-consuming task. In our work we used molecular dynamics (MD) simulations in order to evaluate the applicability of such methods to pre-screening of the packaging material-solute compatibility. The solvation free energy and the free energy of adsorption of diverse solute/solvent/solid systems were estimated. The results of our simulations agree with experimental values previously published in the literature, which indicates that the methods in question can be used to semi-quantitatively reproduce the solid-liquid interactions of the investigated systems.

Drug transport in artery walls: a sequential porohyperelastic-transport approach.

A simulation framework for drug-eluting stents (DES) is presented that simulates the two distinct operational phases of a DES: stent deployment is simulated first, a mechanical porohyperelastic/elasto-plastic/contact analysis. This analysis calculates the interstitial fluid velocity as the result of interstitial fluid pressure gradients and mechanical deformations of the vessel wall. The deformed geometry, interstitial fluid velocity field and porosity field are extracted and used as input for the drug release simulation: a reaction-advection-diffusion (RAD) transport analysis calculating the spatial and temporal drug distribution. The advantage of this approach is that the deformed geometry and interstitial fluid velocity field are not assumed a priori, but are actually calculated using a stent deployment simulation. The framework is demonstrated simulating a DES in an idealised, 3D vessel. Varying mechanical and transport properties based on literature data are assigned to each of the three layers in the wall. The results of the drug release simulation for a period of one week show that the drug distributes longitudinally but will remain in the proximity of the stented area.