1. No category

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




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
2
international
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.
3
international
Changes of State for Water
 Why does water melt? Boil?
 What is HEAT?
4
international
What is sublimation?
5
international
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.
6
international
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
7
international
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.
8
international
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”.
9
international
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
10
international
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.
11
international
Phase Change
12
international
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
13
international
Lyo Operations








Machine Cleaning & Sterilization
Product Loading
Product Freezing
Condenser turned on
Vacuum Draw
Primary Drying: Sublimation
Secondary Drying: Desorption
Vacuum release & stoppering
14
international
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
15
international
Exercise 1.1: Pressure Units







Convert the following:
150 mTorr =
_________ mBar
_________ Pascal
_________ Atmospheres (atm)
_________ PSI (psia)
_________ mmHg
16
international
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?
17
international
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
18
international
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. A pound of snow
b. A pound of steam
19
international
Question 2 of 3

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
20
international
Question 3 of 3
Put the following steps into logical chronology.
______ Vacuum release & stoppering
______ Vacuum Draw
______ Product freezing
______ Condenser turned on
______ Desorption
______ Sublimation
21
international
Module 1 Summary
 Physics of sublimation, heat, and phase
change.
 Examine the essential elements of
Lyophilization
 Review the units used for pressure
measurement.
22
international