Lyotherm is a novel analytical instrument that combines DTA and Impedance Analysis to provide a thorough understanding of a product's freeze drying characteristics.

1. Lyotherm2
Thermal Analyser

2. Lyotherm2
Lyotherm2 is a unique cutting edge technology pioneered
by Biopharma Technology Ltd with the help of Professor
Louis Rey as a solution to some of the most difficult
challenges faced by freeze drying R&D scientists
Biopharma Technology Ltd has used Lyotherm2 to analyse
over 500 different formulations, from small drug molecules to
large complex biomolecules for biopharmaceutical companies
worldwide

3. Differential Thermal Analysis
Measures the difference in temperature
between a sample and a reference as heat
is applied or removed from the system.
This method is sensitive to endothermic
and exothermic processes
Endotherms Exotherms
•Melting •Crystal transitions
•Transitions in the frozen state •Crystallization

4. Impedance Analysis (ZSinφ)
Impedance analysis is fixed frequency
dielectric analysis
It can provide an indication
of the mobility of a sample in
its frozen state, as
demonstrated in a study
carried out by Professor
Louis Rey*
*Freeze-Drying/ Lyophilization of pharmaceutical and biological products. Vol 137, “Drugs and the
pharmaceutical sciences” series. 2nd edition, Eds L. Rey, J.C. May, Marcel Dekker Inc., New York

5. Benefits of Using Lyotherm2
• It can help improve old and develop new
formulations
• It can provide essential data to develop cycles on a
rational scientific basis
• It can save valuable development time and money
• Enables rapid determination of frozen state
behaviour
• Archives data for future reference
• Not limited to freeze-drying research but to all frozen
state applications

6. Advantages
Lyotherm2 performs a similar function to DSC (differential scanning
calorimetry) as it has a built in differential thermal analyser which
identifies significant thermal events.
The advantage of Lyotherm2 is that it combines DTA with an Impedance
Analysis (ZSinφ) function, which can provide an indication of the
mobility of a sample in its frozen state. Thus giving a more complete
picture of the events occurring within your product than thermal analysis
alone.

7. Lyotherm2 System Components

8. System Components
Aluminium heating block
Dewar for rapid
designed to distribute heat
cooling by Liquid
evenly, minimising variation
Nitrogen
between samples
DTA Probes (Sample and Impedance probe
Lyotherm2 Control Box
Reference) (ZSinφ)

9. Assay Procedure
1. Load 3ml samples into 2 individual sample holders
2. Load a 3ml reference (solvent) sample for DTA
analysis
3. Place probes into 4. Place and secure
sample holders sample holders into
block

10. Assay Procedure
5. Initiate data logging
using Lyotherm2 software
6. Lower heating block into
Dewar 1/3 filled with LN2
7. When sample and reference are
below -100°C, switch on heating.

11. Data Recording
Graphical plots of both the ZSinϕ
and DTA values are available
tracking the raw data.
Near-linear cooling rates are
provided by the thermally
distributing design of the sample
holding block.

12. Data Analysis
Real-time analysis of both
ZSinϕ and DTA give results
during the analysis,
updated every 5 seconds.
This provides usable data
before the analysis is
finished.

13. Data Analysis
Electrical Impedance Z (kOhms)
Delta-T (°C) (Endo Down)
The software package
allows you to export
your data directly to
Microsoft Excel for easy
data interpretation and
graph manipulation
Temperature (°C)

14. Problem Solved
‘Trial and Error’ Determination of critical New cycle based
Cycle resulting in temperatures and / or annealing on actual
loss of product step requirement parameters
Lyotherm2 provides you with essential information on the
critical temperatures of your formulation, enabling you to get
the best results from your product

15. Biopharma House, Winnall Valley Road, Winchester SO23 0LD, UK
Tel: +44 (0)1962 841092 Web: www.btl-solutions.net