Module 1: Overview & Fundamentals

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

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.

Changes of State for Water Why does water melt? Boil? http://www.phys.unsw.edu.au/~jw/boiling.html#pressure Talk about Molecular Motion and Energy. What is HEAT?

What is sublimation?

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.

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

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 “.

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”.

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 http://www.school-for-champions.com/science/heat_ice_steam.htm

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.

Phase Change

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

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

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.

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

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? 29.921 in_Hg – 28.4 in_Hg = 1.521 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. > 4.579 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.

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

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

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

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

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