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Henning Gieseler - Articles and news items

Figure 1 Schematic illustration of a particle stabilised by a steric stabiliser. Note that it has been reported that both the degree of adsorption and the density / thickness of the steric barrier are essential factors to mitigate freezing and drying stresses

Stabilisation of nanoparticles during freeze drying: The difference to proteins

Issue 4 2011, Lyophilisation / 31 August 2011 / Jakob Beirowski and Henning Gieseler, University of Erlangen-Nuremberg, Division of Pharmaceutics, Freeze Drying Focus Group

The underlying concept for the stabilisation of proteins during freeze drying is the formation of a glassy matrix in which the macromolecules remain isolated and immobilised. The concept relies on the so-called ‘vitrification hypothesis’ which assumes that the formation of an amorphous phase by lyoprotectants is mandatory to interact with the amorphous protein molecule. The use of lyoprotectants has also been found to be beneficial to preserve the original particle size distribution of nanoparticles during freeze drying. Until today, it has been speculated that the predominant mechanism to suppress physical instabilities of such colloidal particle systems is their embedment in a rigid glass. Today, there are various types of colloidal particles used in drug development, and sometimes the scientific literature gives evidence that glass formation was not necessarily required for stabilisation during freezing thawing or even freeze drying. The purpose of this article is therefore to briefly provide the latest insight into potential stabilisation mechanisms when freeze drying nanoparticles, a key knowledge for rational formulation and process design for such systems.

Process Analytical Technology (PAT) in Freeze Drying: Tunable Diode Laser Absorption Spectroscopy as an evolving tool for Cycle Monitoring

Issue 6 2009, Past issues / 12 December 2009 /

The most important critical product parameter during a freeze-drying process is the product temperature at the ice sublimation interface, Tp1. Once the product temperature in this area of interest exceeds the critical formulation temperature (typically denoted as “collapse temperature”, Tc) during primary drying, a stepwise loss of the cake structure may be observed2,3. This, in turn, can greatly impact the product quality attributes with regard to product appearance, reconstitution times, sub-visible particles and residual moisture content4.

Application of DSC and MDSC in the development of freeze dried pharmaceuticals

Issue 6 2008, Past issues / 3 December 2008 / Jakob Beirowski, Pharmacist and Dr. Henning Gieseler, Assistant Professor, Division of Pharmaceutics, University of Erlangen-Nuremberg

Freeze drying of pharmaceuticals requires an adequate formulation design to prevent low-temperature, freezing and drying stresses. The goal is to achieve a final product with long storage stability and elegant appearance. To meet these specifications the product temperature must be controlled below the critical formulation temperature during the freeze drying cycle. DSC is an established tool to measure this critical formulation property in the development of freeze dried pharmaceuticals as it allows rapid sample preparation and analysis time. The introduction of modulated DSC (MDSC) by Reading in 1992 has greatly facilitated the interpretation of DSC results. The overlapping transitions in the same temperature range can be distinguished and characterisation of the nature of transitions is facilitated.

A significant comparison between collapse and glass transition temperatures

Issue 5 2008, Past issues / 29 September 2008 /

Rational freeze-drying process design is based on a representative and accurate measurement of the critical formulation temperature. To avoid product shrinkage or collapse, it is indispensable to control the product temperature just below this key temperature during primary drying. Over the last decades, DSC was routinely used to determine the glass transition temperature of the maximally freeze concentrated solute (Tg’), information which was then applied to freeze-drying process design. Recently, Freeze-Dry Microscopy (FDM) was introduced as a new technology to determine an even more representative critical temperature: the collapse temperature (Tc). Today, important technological improvements in FDM even allow more sophisticated observations of collapse behaviour and therefore, further cycle optimization.

PAT for freeze drying: cycle optimisation in the laboratory

Issue 1 2007, Past issues / 25 January 2007 / Dr. Henning Gieseler, PhD., Department of Pharmaceutics, University of Erlangen-Nuremberg

Freeze drying is generally known to be a time consuming and therefore expensive process. In order to lower costs during manufacturing, the effective cycle time must be reduced. This goal can be achieved by optimising a freeze drying cycle in the laboratory – in particular the primary drying phase. Applying PAT in the laboratory can provide valuable information about product and process behaviour and may help to identify the critical process parameters during cycle development and optimisation.

 

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