Mirror symmetric broadband homodecoupled perfect echo spectroscopy.

A new experiment for recording phase sensitive ω-broadband homodecoupled TOCSY spectra is presented. The method is an extension of the already existing perfect echo (PE) filter, proposed to sample t chemical shift under sustained homodecoupling. The modification is made by attaching a time reversed perfect echo filter to a regular perfect echo scheme.

An example of how to establish the thermodynamic stability relationship between two polymorphs of a compound highly prone to solvate formation.

Upon transition from research to development, a new chemical entity, which acts upon the Kv1.5-potassium channel and blocks potassium flow in the atrium of the human heart, has been subjected to a crystallization screen. The sodium salt of an anthranilic acid amide with a heteroarylsulfonyl side chain forms solvates from all tested organic solvents.

The quaternary structure of insulin glargine and glulisine under formulation conditions.

The quaternary structures of insulin glargine and glulisine under formulation conditions and upon dilution using placebo or water were investigated using synchrotron small-angle X-ray scattering. Our results revealed that insulin glulisine in Apidra® is predominantly hexameric in solution with significant fractions of dodecamers and monomers. Upon dilution with placebo, this equilibrium shifts towards monomers.

Rapid-Acting and Human Insulins: Hexamer Dissociation Kinetics upon Dilution of the Pharmaceutical Formulation.

Purpose: Comparison of the dissociation kinetics of rapid-acting insulins lispro, aspart, glulisine and human insulin under physiologically relevant conditions.

Methods: Dissociation kinetics after dilution were monitored directly in terms of the average molecular mass using combined static and dynamic light scattering. Changes in tertiary structure were detected by near-UV circular dichroism.

Stabilization of Insulin by Adsorption on a Hydrophobic Silane Self-Assembled Monolayer.

The interaction between many proteins and hydrophobic functionalized surfaces is known to induce β-sheet and amyloid fibril formation. In particular, insulin has served as a model peptide to understand such fibrillation, but the early stages of insulin misfolding and the influence of the surface have not been followed in detail under the acidic conditions relevant to the synthesis and purification of insulin. Here we compare the adsorption of human insulin on a hydrophobic (-CH3-terminated) silane self-assembled monolayer to a hydrophilic (-NH3(+)-terminated) layer.

The evolution of insulin glargine and its continuing contribution to diabetes care.

The epoch-making discovery of insulin heralded a new dawn in the management of diabetes. However, the earliest, unmodified soluble insulin preparations were limited by their short duration of action, necessitating multiple daily injections. Initial attempts to protract the duration of action of insulin involved the use of various additives, including vasoconstrictor substances, which met with limited success.

Characterization and evaluation of a modified PVPA barrier in comparison to Caco-2 cell monolayers for combined dissolution and permeation testing.

Aim of this study was to implement a modified phospholipid vesicle-based permeation assay (PVPA) barrier as alternative to Caco-2 cell monolayers in a combined dissolution and permeation system for testing of solid dosage forms. Commercially available Transwell® inserts were coated with egg phospholipids (Lipoid E 80) and characterized by confocal Raman microscopy. The modified PVPA barrier was then evaluated in permeation studies with solutions of different drugs as well as in combined dissolution and permeation studies utilizing an immediate and an extended release tablet formulation.