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.

Assessment of powder blend uniformity: Comparison of real-time NIR blend monitoring with stratified sampling in combination with HPLC and at-line NIR Chemical Imaging.

Scope of the study was (1) to develop a lean quantitative calibration for real-time near-infrared (NIR) blend monitoring, which meets the requirements in early development of pharmaceutical products and (2) to compare the prediction performance of this approach with the results obtained from stratified sampling using a sample thief in combination with off-line high pressure liquid chromatography (HPLC) and at-line near-infrared chemical imaging (NIRCI). Tablets were manufactured from powder blends and analyzed with NIRCI and HPLC to verify the real-time results. The model formulation contained 25% w/w naproxen as a cohesive active pharmaceutical ingredient (API), microcrystalline cellulose and croscarmellose sodium as cohesive excipients and free-flowing mannitol.

An integrated early formulation strategy--from hit evaluation to preclinical candidate profiling.

The selection of a suitable vehicle for preclinical compound profiling is a very important task during the early developmental phases to ensure the quality of candidates and the speed of compound progression. Apart from biopharmaceutical and pharmaceutical technical considerations, i.e.