Module 1: Overview & Fundamentals

Module 1:
Overview & Fundamentals
© Institute for International Research, Inc. 2006. All rights reserved.
Module 1 Purpose and Objectives
 Module Purpose:
 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
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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
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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.
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Changes of State for Water
 Why does water melt? Boil?
 What is HEAT?
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What is sublimation?
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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.
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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
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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
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.
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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”.
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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
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Specific Heats
 Ice: 2.09 J / (gm∙C)
 Water: 4.187 J / (gm∙C)
 Steam: 1.989 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.
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Phase Change
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Sublimation
Heat of Sublimation Calculated from
1. The melting of ice: Heat of Fusion
2. The rise in Temperature of Water: Specific
Heat of Water – Not Used – No water happens.
3. The boiling of Water: Heat of Vaporization
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Lyo Operations
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Machine Cleaning & Sterilization
Product Loading
Product Freezing
Condenser turned on
Vacuum Draw
Primary Drying: Sublimation
Secondary Drying: Desorption
Vacuum release & stoppering
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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
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Exercise 1.1: Pressure Units
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Convert the following:
150 mTorr =
_________ mBar
_________ Pascal
_________ Atmospheres (atm)
_________ PSI (psia)
_________ mmHg
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Exercise 1.1: Pressure Units
 An operator reports that the vacuum
gauge on the lyophilizer reads -28.4
inches. What does that mean? i.e. What
would be the temperature of an ice
interface that was being lyophilized at
that vapor pressure?
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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
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Question 1 of 3
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Quiz Question
Assume 1 atm and Snow Temp = -5C
and Steam Temp = 100C.
Which contains the higher heat?
a. A pound of snow
b. A pound of steam
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Question 2 of 3
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The Heat of Sublimation is
A. Heat of Fusion + Heat of Vaporization
B. Heat of Fusion + Specific Heat * T + Heat
of Vaporization
C. The Rate of Temperature change that
induces ice to turn into a gas.
D. Heat of Vaporization + the Heat in the Ice
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Question 3 of 3
Put the following steps into logical chronology.
______ Vacuum release & stoppering
______ Vacuum Draw
______ Product freezing
______ Condenser turned on
______ Desorption
______ Sublimation
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Module 1 Summary
 Physics of sublimation, heat, and phase
change.
 Examine the essential elements of
Lyophilization
 Review the units used for pressure
measurement.
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