Lyophilization

Question 1

Moisture Removal
by
Sublimation

To Improve stability caused by moisture degradation

Answer 1

Lyophilization

Control of temperature & pressure
needed

Question 2

Non-Pharmaceutical Applications
of
Lyophilization

Answer 2

Food Preservation / Products
Coffee / NASA - freeze dried

• *Restoration** from moisture damage
• *Paper / Paintings**

Museum Pieces

Animal Specimens

Wedding Flowers

Question 3

Pharmaceutical Applications

​Lyophilization

Answer 3

Drug ISOLATION
from solution - research state

Lyophilized Drug Products

Sterile Powder
for manufaturing poweder filling

Question 4

Chamber - Tight Seal

• *Freezing Capability**
• *-50***
• *Vacuum Pump
• LOW PRESSURE = ~50 microns***

Heating Capability

CONDENSER

Answer 4

Req for FREEZE DRYING

Question 5

Conduction
contact

Convection
air –> blowing

Radiation
from the sun / em waves

Answer 5

Mechanisms of

HEAT TRANSFER

Question 6

Typical Lyophilization Pressure

Answer 6

100-500 microns

VERY LOW VACUUM

Drop in Pressure –> allow for sublimation

Question 7

Vacuum Pressure

1 atm = ?

Answer 7

1atm = 760 mm = 760 torr

= 760k microns

typical lyo pressure = 100-500 microns

Question 8

HIGHER THE PRESSURE
effect on heat transfer / rate of sublimation

Answer 8

BETTER the Heat transfer by CONDUCTION

SLOWER the rate of SUBLIMATION

Question 9

Triple Point

Answer 9

TEMP & PRESSURE
@
which a substance can exist in

LIQUID / SOLID / GASEOUUS STATE

Question 10

Triple Point of Water

Answer 10

0.01*C
&
4.58mm
of mercury is used to calibrate thermometors

Question 11

Water Liquid
V
Water ICE
V
Water GAS
very slow heating under _vacuum_
remove moisture
do not want it to BOIL

Answer 11

Lyophilization process

Question 12

LYO Process for a
PHARMACEUTICAL PRODUCT

Answer 12

STERILE FILTRATION

1. Drug is in solution =
   
   1. WATER LIQUID
2. Fill drug product solition –> vials
3. FREEZING –> 30* (below triple point) = annealing
   
   1. WATER ICE
4. ​VACUUM –> reduce pressure to microns
5. HEAT –> heat product to accelerate sublimation (drying) & remove adsorbed moisture (secondary drying
   
   1. WATER GAS
6. ​Capping​​

Question 13

Preformulation Studies - API Charterization

of LYO’s

Answer 13

POLYMORPHISM
SOLID STATE

Solubility
pH effects / ionization
insoluble drug –> soluble @ diff pH

STABILITY

Density / Hygroscopicity / Flowability

Compressibility / Wettability

Question 14

Lyophilized Pharm Products

Answer 14

Appearance

Formulation

Bulk Lyophilization

Powder Filled

Lyophilization in VIAL

Cleaning the Lyophilizer

Question 15

What does a powder product
(lyophilized or crystalized) tell you?

Answer 15

That the product is

LIKELY UNSTABLE IN SOLUTION

have to reconstitute

how long is it stable?

Question 16

Conduction

Answer 16

CONTACT

form of heating

Question 17

Condenser FUNCTION

Answer 17

Used in the
Heating / Drying
last step of lyophilization

Condenser has to be COLDER than the VIAL
vapor water in vial –> condenser
to be the driving force
vapor pressure has to be LESS

vapor pressure (proportional to) temperature