Application of Imaging Techniques to Cases of Drug-Induced Crystal Nephropathy in Preclinical Studies.

A number of drugs can cause precipitates within renal tubules leading to crystal nephropathy. Crystal nephropathy is usually an exposure-related finding and is not uncommon in preclinical studies, where high doses are tested. An understanding of the nature of precipitates is important for human risk assessment and further development.

Rapid assessment of homogeneity and stability of amorphous solid dispersions by atomic force microscopy--from bench to batch.

Purpose: To verify the robustness and fundamental value of Atomic Force Microscopy (AFM) and AFM-based assays to rapidly examine the molecular homogeneity and physical stability of amorphous solid dispersions on Hot-Melt-Extrudates.

Methods: Amorphous solid dispersions were prepared with a Hot-Melt Extruder (HME) and profiled by Raman Microscopy and AFM following a sequential analytical routine (Multi-Scale-Imaging-of-Miscibiliy (MIMix)). Extrudates were analyzed before and after incubation at elevated temperature and humidity.

Miniaturized screening of polymers for amorphous drug stabilization (SPADS): rapid assessment of solid dispersion systems.

Purpose: Development of a novel, rapid, miniaturized approach to identify amorphous solid dispersions with maximum supersaturation and solid state stability.

Method: Three different miniaturized assays are combined in a 2-step decision process to assess the supersaturation potential and drug-polymer miscibility and stability of amorphous compositions. Step 1: SPADS dissolution assay.

Atomic force microscopy-based screening of drug-excipient miscibility and stability of solid dispersions.

Purpose: Development of a method to assess the drug/polymer miscibility and stability of solid dispersions using a melt-based mixing method.

Methods: Amorphous fractured films are prepared and characterized with Raman Microscopy in combination with Atomic Force Microscopy to discriminate between homogenously and heterogeneously mixed drug/polymer combinations. The homogenous combinations are analyzed further for physical stability under stress conditions, such as increased humidity or temperature.

Evidence for heterodimers of 2,4,5-trichlorophenol on planar lipid layers. A FTIR-ATR investigation.

Trichlorophenols are weak acids of high hydrophobicity and are able to transport protons across the mitochondrial membrane. Thus the proton motive force is dissipated and the ATP production decreased. In situ Fourier Transform Infrared-Attenuated Total Reflection (FTIR-ATR) experiments with 2,4,5-trichlorophenol (TCP) adsorbed to model membranes resulted in good evidence for the formation of the TCP-heterodimer.