Evaluating the inter and intra batch variability of protein aggregation behaviour using Taylor dispersion analysis and dynamic light scattering.

Biosimilar pharmaceuticals are complex biological molecules that have similar physicochemical properties to the originator therapeutic protein. They are produced by complex multi-stage processes and are not truly equivalent. Therefore, for a biosimilar to be approved for market it is important to demonstrate that the biological product is highly similar to a reference product.

A discriminatory intrinsic dissolution study using UV area imaging analysis to gain additional insights into the dissolution behaviour of active pharmaceutical ingredients.

For efficient and effective drug development it is desirable to acquire a deep understanding of the dissolution behaviour of potential candidate drugs and their physical forms as early as possible and with the limited amounts of material that are available at that time. Using 3-10mg sample quantities, the ability of a UV imaging system is investigated to provide deep mechanistic insight into the intrinsic dissolution profiling of a range of compounds and physical forms assessed under flow conditions. Physical forms of indomethacin, theophylline and ibuprofen were compressed and their solid-state form confirmed before and after compression with X-ray methods and/or Raman spectroscopy.

Taylor dispersion analysis compared to dynamic light scattering for the size analysis of therapeutic peptides and proteins and their aggregates.

Purpose: To evaluate Taylor dispersion analysis (TDA) as a novel method for determination of hydrodynamic radius of therapeutic peptides and proteins in non-stressed and stressed formulations and to compare it with dynamic light scattering (DLS).

Methods: The hydrodynamic radius of oxytocin, bovine serum albumin, various monoclonal antibodies (type IgG) and etanercept at concentrations between 0.05 and 50 mg/ml was determined by TDA and DLS.

A nanolitre method to determine the hydrodynamic radius of proteins and small molecules by Taylor dispersion analysis.

The escalating number of new therapeutic biopharmaceuticals being developed and their high value increases the need for the development of novel analytical technologies. Faster analysis time, high accuracy, low sample consumption and the ability to monitor process flow are all essential prerequisites. We evaluate a novel analytical instrument that combines UV area imaging and Taylor dispersion analysis (TDA) to determine the hydrodynamic radius of proteins and small molecules in solution.

Influence of protein on mannitol polymorphic form produced during co-spray drying.

The stabilizing ability of the excipient on pharmaceutically relevant proteins for potential therapeutic use is an extensive area of research but the effect the protein has on the excipient is rarely reported. The influence of two model proteins on the polymorphic behaviour of mannitol during spray drying was therefore investigated. Spray dried mannitol/protein blends were characterised structurally using X-ray powder diffraction (XRPD) and Fourier transform Raman spectroscopy (FT-Raman) and thermally by differential scanning calorimetry (DSC) and also thermogravimetric analysis (TGA).

The characterization and comparison of spray-dried mannitol samples.

Background: Following the production of spray-dried mannitol powders, it is essential that the polymorphic content of each individual product is completely characterized. The implications of the polymorphic behavior of mannitol are immense. The appearance or disappearance of a crystalline form within a dosage form can have costly repercussions and lead to a dosage form being withdrawn.

Do co-spray dried excipients offer better lysozyme stabilisation than single excipients?

The inherent instability of proteins when isolated from their native conditions creates the necessity of suitable stabilisation techniques. Because of the instability of proteins in solution it is often necessary to produce them as solid formulations. A method of producing relatively stable, solid protein pharmaceuticals is to incorporate them with a suitable excipient into an amorphous matrix by dehydration.

The impact of low-level inorganic impurities on key physicochemical properties of paracetamol.

Trace inorganic impurities in active pharmaceutical ingredients (APIs) while having limited toxicological significance might affect the down stream processing properties of those substances. The level of impurities in paracetamol batches was quantified and mapped using inductively coupled polarization mass spectrometry (ICP-MS) and scanning electron microscopy coupled with energy dispersive X-ray microanalysis (SEM-EDX). The physical form of samples was assessed using X-ray powder diffraction (XRPD) and characterised thermally using differential scanning calorimetry (DSC) and thermogravimetric analysis (TGA).