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Thermal Analysis - Articles and news items

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Purity Determination of Pharmaceuticals by Thermal Analysis

Webinars / 4 February 2016 /

In this Webinar, we will discuss the basic principles of DSC purity determination and present some interesting applications…

Application Note: Morphological changes in drug compounds under the microscope

Application Note: Morphological changes in drug compounds under the microscope

Whitepapers / 15 January 2016 / Dr. Matthias Wagner, Product Manager, Mettler Toledo

Heated crystalline pharmaceutical compounds undergo morphological changes that can be observed under a microscope. With hot-stage microscopy changes in melting points and ranges or crystallisation can be visualised for research and QC purposes in order to influence drug stability or effectiveness…

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The 9 validation steps required for thermal analysis method validation in an analytical laboratory

Webinars / 2 December 2015 /

In this Webinar, we discuss the basic principles of validation, from equipment qualification and computerised system validation through to analytical method validation…

DSC is the most frequently used thermal analysis technique

Principles of Differential Scanning Calorimetry (DSC) – the most used thermal analysis technique in pharmaceuticals

Webinars / 18 September 2015 /

In this Webinar, we discuss the basic principles of Differential Scanning Calorimetry (DSC) – the most used thermal analysis technique in pharmaceuticals…

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Mettler Toledo introduces new high performance Thermal Analysis products for premium results

Supplier news / 10 August 2015 / Mettler Toledo

METTLER TOLEDO is pleased to introduce two new products to the Thermal Analysis Premium portfolio, the DSC3+ and TGA/DSC 3+, for superior results on the most demanding applications…

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Basics of calibration and adjustment in Thermal Analysis – Useful tips and hints

Webinars / 13 July 2015 / Mettler Toledo

In this webinar, we discuss the basics of calibration and adjustment in thermal analysis whilst offering some useful tips and hints…

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Investigation of pharmaceutical substances by thermal analysis

Webinars / 26 April 2015 /

Our experts demonstrate how thermal analysis is used to investigate pharmaceutical substances, presenting some typical examples measured by DSC, TGA, TMA or DMA…

Figure 3: The global TSC spectrum of caffeine Form I

Applications of thermally stimulated current spectroscopy in pharmaceutical research

Issue 3 2012, Thermal Processing / 10 July 2012 / Milan Antonijević, School of Science, University of Greenwich

Thermally Stimulated Current Spectroscopy (TSC) is a new tool that can be used to analyse pharmaceutically important molecules. TSC studies are usually conducted to provide additional information about molecular mobility in the solid state, and as a result characterise phase transitions that are related to thermal transitions in the crystalline (polymorphic) and amorphous phases. The ability of TSC to probe molecular mobilities, previously undetected in materials, and link them to the stability of different phases has sparked immense scientific interest in this technique.

In the last 10 years, the pharmaceutical market has seen a significant decrease in approved new drug entities. Although many factors may be responsible for this trend, one of them is insufficient information / characterisation of a lead molecule. Consequently, new techniques are often applied in the pharmaceutical field with the simple goal to aid better selection of the drug candidate and dosage form.

Improving the performance of existing drug products is another goal that often requires comprehensive information about the properties of the drug molecules. In recent years, the physical sciences have made great progress towards understanding the properties of pharmaceutically important amorphous and polymorphic materials. The major focus of this work is to utilise the advantages that they may bring to formulated products (e.g. faster solubility of amorphous drugs compared to crystalline counterparts) and at the same time to overcome stability problems (e.g. tendency to recrystallise on storage) that they may demonstrate.

Figure 1 Free energy diagram for a single step binding interaction between protein (P) and ligand (L). For a binding reaction of this type increasing affinity is achieved by lowering the free energy of the PL complex. Increasing residence (decreasing koff) time is achieved by lowering the free energy of the PL complex and/or destabilizing the transition state

Thermodynamics and kinetics driving quality in drug discovery

Issue 4 2011, Thermal Processing / 31 August 2011 / Geoff Holdgate, AstraZeneca

Recently, there has been renewed interest in using thermodynamic and kinetic data, alongside empirical rules (particularly focused upon cLogP and molecular weight) and guiding metrics such as ligand efficiency and lipophilic ligand efficiency developed for fragments, leads and drugs in order to facilitate the design of compounds with a greater chance of producing successful drugs1. This interest has been assisted both by improvements in instrumentation as well as evidence that thermodynamically and kinetically optimised compounds fare better in the clinic2.

Optimisation of the binding affinity, which may have to be improved by several orders of magnitude from initial hit to drug molecule, can be achieved by modifying the individual thermodynamic and kinetic contributions. However, medicinal chemists have, up to now, been reluctant to consider these measurements during hit selection and lead optimisation, because it has been difficult to understand how the different design strategies affect the individual forces resulting in different thermodynamic and kinetic profiles. By incorporating both retrospective analysis and real time data collection in active projects, the value of using these fundamental contributions to guide the selection of chemical start points and how they can be used to influence optimisation strategies will become clear.

ITC: affinity is not everything

Issue 1 2009, Past issues / 7 February 2009 /

During the optimisation of drug candidates, improvements in affinity and selectivity play a critical role. This task is usually accomplished by establishing accurate correlations between the affinity/selectivity of different chemical scaffolds and through chemical modifications to a selected scaffold.

Fast-scan differential scanning calorimetry

Issue 4 2008, Past issues / 2 August 2008 /

Differential scanning calorimetry (DSC) is a widely used technique within the pharmaceutical industry because the range of phase transitions it can measure usually allows near complete physical characterisation of a new active principal early during preformulation. In addition, because DSC measures a property change that is ubiquitous† (heat) there are very few samples that cannot be investigated.

Thermal analysis and calorimetry: latest developments

Issue 2 2008, Past issues / 19 March 2008 /

Thermal analysis techniques cover all methods in which a physical property is monitored as a function of temperature or time, whilst the sample is being heated or cooled under controlled conditions. Calorimetric methods measure the energy involved in every process. The quicker new developments attain the market, such as the progression of micro or nanotechnologies, combinations of different hyphenated techniques, as well as the development of high automated or high throughput systems, the faster new horizons will open in the industrial environment. In addition, the application of sophisticated kinetic software in DSC, calorimetry and reaction calorimetry gives better safety predictions.

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