Nosheen Mehmood's Assignment

LYOPHILIZATION TECHNOLOGY

Product, Process & Systems

Name : Nosheen Mehmood PHYSICAL PHARMACEUTICS
Roll No. : S19PHM01 Pharm-D (BATCH 2)

LYOPHILIZATION

freeze drying is a process in which water is removed from a product a er it is frozen and
placed under a vacuum, allowing the ice to change directly from solid to vapor without
passing through a liquid phase ( through process of sublima on).
Freeze drying results in a high-quality product because of the low temperature used in
processing. The original shape of the product is maintained and quality of the rehydrated
product is excellent. Primary applica ons of freeze drying include biological
(e.g., bacteria and yeasts), biomedical (e.g., surgical transplants), food processing
(e.g., coffee).

Name : Nosheen Mehmood 1
Roll No. : S19PHM01

PRIMARY DRYING

The drying portion of freeze drying is actually a two part process consisting
of Primary Drying and Secondary Drying. The bulk of water removed from the
product during freeze drying is via sublimation of all of the free ice crystals
during the primary drying step. Organic solvents are also removed during
primary drying.

Primary drying (sublimation) is a slow process conducted at cooler temperatures,
safely below the product’s critical collapse temperature. Sublimation requires
heat energy to drive the phase change process from solid to gas.
All three methods of heat transfer - conduction, convection and radiation,
must be considered when freeze drying a product.

In a simple manifold dryer, heat is transferred to the flask/product primarily
through convection and radiation from the surrounding environment. With little
control over heat flow into the product, it is more difficult to control the process.
When working with products with low collapse temperatures.

Name : Nosheen Mehmood 2
Roll No. : S19PHM01

SECONDARY DRYING

In addition to the free ice that is sublimed during primary drying, there remains
a substantial amount of water molecules that are bound to the product. This is
the water that is removed (desorbed) during secondary drying. Since all of the
free ice has been removed in primary drying, the product temperature can now
be increased considerably without fear of melting or collapse.

Secondary drying actually starts during the primary phase, but at elevated
temperatures (typically in the 30ºC to 50ºC range), desorption proceeds much
more quickly. Secondary drying rates are dependant on the product temperature.
System vacuum may be continued at the same level used during primary drying;
lower vacuum levels will not improve secondary drying times.

Amorphous products may require that the temperature increase from primary to
secondary drying be controlled at a slow ramp rate to avoid collapse.

Name : Nosheen Mehmood 3
Roll No. : S19PHM01

Pharmaceutical Lyophilization Systems

Freeze drying or lyophiliza on is applied to pharmaceu cal research, development,
manufacturing, and transport. Lyophiliza on in the development of biopharmaceu cals
revolves around the process of sublimina on, by which proteins, an bodies, or other
drug and drug-related substances are converted from a solid phase directly to a
gaseous phase. Freeze drying is commonly employed to overcome barriers to stability
in labile products and common uses of lyophiliza on are seen in the crea on and
storage of room temperature products. Freeze-dried products’ extended shelf lives
provide benefits for research and manufacturing.

Name : Nosheen Mehmood 4
Roll No. : S19PHM01

Advantages of Lyophilization

Disadvantages of Lyophilization

Name : Nosheen Mehmood 5
Roll No. : S19PHM01

Applications and Benefits

1. Modern, user-friendly software allowing robust simulations, parameter estimation, graphical outputs,
sensitivity analysis and optimization. No coding is required by user.

2. Straightforward workflow for process development and sequential evaluation of key adjustable parameters
of the models: heat transfer coefficient and mass transfer coefficient

3. Practical methodology for process transfer and scale-up or scale-down, modification and optimisation

4. Single vial and vial packing approaches with separate models for sublimation of pure water from a single
vial or packing of vials. The models allow fast evaluation apparent heat transfer coefficients at critical locations
on a shelf
5. Explore process design and decision space to systematically analyse the impact of process conditions on
operation using Global System Analysis tool

Scale-up from lab-scale to large-scale freeze drying cycles

The diagram below is a gPROMS FormulatedProducts workflow that enables faster tech transfer and
optimisation with reduced experimentation for lyophilization processes.

Name : Nosheen Mehmood 6
Roll No. : S19PHM01

Thanks

Name : Nosheen Mehmood 7
Roll No. : S19PHM01