1. Module 1: Overview & Fundamentals

2. Module 1 Purpose and Objectives
The attendee will gain a familiarity with the science and the equipment and how they complement one another.
Module Objectives:
After this module, you will be able to
Understand basic thermodynamics of sublimation
Identify the major operations of lyophilization
Name a few of the important vendors
Identify the major parts of a lyophilizer

3. What is Lyophilization?
Lyophilization is the sublimation of water (usually) away from non-volatile solutes. It is most commonly performed for pharmaceutical products which are maintained frozen throughout the sublimation.
Machine driven sublimation is most often followed by desorption of product associated water and that process is considered a part of the lyophilization.

4. Changes of State for Water
Why does water melt? Boil?
Talk about Molecular Motion and Energy.
What is HEAT?

5. What is sublimation?

6. Conditions for Sublimation
Humidity
Sublimation of Snow. [The opposite of sublimation might be snow formation]
Partial Pressure of Water in the Air
Dalton’s Law: The Pressure of a GAS is equal to the sum of the pressures of the individual components of the gas.

7. What is P(water) in Air
At atmospheric pressure (1 atm) we can look at varying relative humidity (x axis) and let air temperature vary over time (-10  C to 0C)
Y Axis is Partial Pressure of Water
100% RH is Water Vapor Saturation

8. P(water) in Air
When the air temperature is below freezing, most RH values are at a level where sublimation can occur.
Temp C
Pressure Of
Sublimation
-10
260 Pa -5
402 Pa -9
284 Pa -4
437 Pa -8
310 Pa -3
476 Pa -7
338 Pa -2
517 Pa -6
369 Pa -1
562 Pa
At Partial Pressures below these values, Sublimation will occur.
To assure that the “partial pressure” is below the “partial vapor pressure needed for sublimation” one can get the total pressures lower than the “partial vapor pressure needed for sublimation “.

9. Specific Heat Heat adds kinetic energy to substances
Substance Temperature increases until it reaches a melting point or boiling point or sublimation point. “Specific Heat” is the Rate of that Temperature Change.
At those points, the temperature remains constant while the substance absorbs heat and melts, boils, or sublimes. This heat is called “Latent heat”.

10. Latent Heats* Heat of Fusion (Ice to Water)
334 Joules / gram
144 BTU / lb
Heat of Vaporization (Water to Steam)
2258 Joules / gram
971 BTU / lb
Heat of Sublimation (Ice to Steam)
3011 Joules / gram
1294 BTU / lb
*Values vary slightly from different sources

11. Specific Heats Ice: 2.09 J / (gm∙C) Water: 4.187 J / (gm∙C)
Steam: J / (gm ∙C)
These are the heats (at 1 atm) that must be put into the substance to raise its temperature without melting, boiling, or sublimation.

12. Phase Change

13. Sublimation Heat of Sublimation Calculated from
The melting of ice: Heat of Fusion
The rise in Temperature of Water: Specific Heat of Water – Not Used – No water happens.
The boiling of Water: Heat of Vaporization

14. Lyo Operations Machine Cleaning & Sterilization Product Loading
Product Freezing
Condenser turned on
Vacuum Draw
Primary Drying: Sublimation
Secondary Drying: Desorption
Vacuum release & stoppering

15. Exercise 1.1: Pressure Units
Participant Exercise Directions:
Use a table for vapor pressure over ice versus temperature of the ice. Determine the steam vapor pressure for the following ice temperatures:
-50C: Pressure = _________ microns
-36C: Pressure = _________ mTorr
-18C: Pressure = _________ mmHg
As a handout, I should provide a Saturation Table and extensive conversion formula.
As part of the exercise, we should cover how to use the conversion formula.

16. Exercise 1.1: Pressure Units
Convert the following:
150 mTorr =
_________ mBar
_________ Pascal
_________ Atmospheres (atm)
_________ PSI (psia)
_________ mmHg

17. Exercise 1.1: Pressure Units
An operator reports that the vacuum gauge on the lyophilizer reads inches. What does that mean? i.e. What would be the temperature of an ice interface that was being lyophilized at that vapor pressure?
in_Hg – 28.4 in_Hg = in_Hg (stated positively from zero absolute).
1.521 in_Hg x 25.4 torr/in_Hg = 36.6 torr.
That is such a high pressure that it is in the melting range for ice (i.e. > torr), therefore the answer is that the ice could not lyophilize and if it is, then the gauge is reporting in error. For that type of gauge, it is likely that it is reporting in error since it would be reading at an extreme end of its intended scale.

18. Module 1 Quiz Participant Directions: Divide into pairs
Take 5 minutes to complete quiz
Correct answers will be reviewed as a large group during debrief

19. Question 1 of 3 Quiz Question
Assume 1 atm and Snow Temp = -5C and Steam Temp = 100C.
Which contains the higher heat?
A pound of snow
A pound of steam

20. Question 2 of 3 The Heat of Sublimation is
Heat of Fusion + Heat of Vaporization
Heat of Fusion + Specific Heat * T + Heat of Vaporization
The Rate of Temperature change that induces ice to turn into a gas.
Heat of Vaporization + the Heat in the Ice

21. Question 3 of 3 Put the following steps into logical chronology.
______ Vacuum release & stoppering
______ Vacuum Draw
______ Product freezing
______ Condenser turned on
______ Desorption
______ Sublimation

22. Module 1 Summary Physics of sublimation, heat, and phase change.
Examine the essential elements of Lyophilization
Review the units used for pressure measurement.