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Chapter 21: Rational Design of a Freeze-Drying Process for Protein Products

  • Feroz JameelEmail author
  • Tong Zhu
  • Ehab M. Moussa
  • Brittney J. Mills
Chapter
  • 69 Downloads
Part of the AAPS Advances in the Pharmaceutical Sciences Series book series (AAPS, volume 35)

Abstract

Freeze-drying is a commonly used manufacturing operation for biopharmaceuticals to enhance the storage stability. The stability of the product during freeze-drying and upon storage depends on the design of the formulation and the freeze-drying process. The robustness of the freeze-drying process is dictated by the formulation composition and the nature of the excipients. In this chapter, the underlying principles and concepts involved in the design of the formulation and the process are discussed and illustrated with a case study. In addition, a novel approach using predictive modeling for the initial guesses of the input parameters of the process is discussed.

Keywords

Lyophilization Freeze-drying Freezing Primary drying Scale-up Manufacturing 

Nomenclature

Pch

Chamber pressure

Psub

Sublimation front pressure

Pref

Reference pressure

Tsh

Shelf temperature

Tsurf

Average shelf surface temperature

Tinlet

Shelf heating fluid inlet temperature

Tbot (or Tb, Tpr)

Product bottom temperature

Te  

Eutectic melting temperature

Tc

Collapse temperature

Tref

Reference temperature

Tcrit

Critical product temperature

Tsh, crit

Critical shelf temperature

Tg  

Glass transition temperature of the dry powder

Tg  

Glass transition temperature of the maximum freeze-concentrated solution

Wg  

Residual unfrozen water content at the Tg′ temperature

\( {\dot{Q}}_{\mathrm{cond}} \)

Heat conduction rate in the frozen product

\( {\dot{Q}}_{\mathrm{tot}} \)

Total heat transfer rate to the vial

\( {\dot{Q}}_{\mathrm{sub}} \)

Heat transfer rate at the sublimation front

Kv

Vial heat transfer coefficient in general

Kv, surf

Vial heat transfer coefficient between the shelf surface and the vial bottom

Kv, inlet

Total/apparent heat transfer coefficient between the shelf fluid inlet and the vial bottom

Krad 

Radiative heat transfer coefficient to the vial from the surroundings

Kgas 

Gas conductive heat transfer coefficient between the vial bottom and the shelf/tray

KC

Pressure independent part of heat transfer coefficient between the vial and the shelf/tray

KP

Constant parameter expressing the pressure dependence of heat transfer coefficient

KD

Pressure dependence of heat transfer coefficient specific to a vial geometry

Rp

Area-normalized product resistance

Rp,max

Maximum area-normalized product resistance for a given product

csolid%

Solid concentration of the formulation (w/v)

R

Universal gas constant

ΔHs

Latent heat of ice sublimation

Ap

Bottom area of the frozen product

Av

Outer area of the vial cross section

lbot

Effective gap distance between the vial bottom and the shelf/tray

lpr, 0

Initial frozen product thickness

lck

Dried cake thickness

Vvill

Fill volume

kice

Heat conductivity of the frozen product

σ

Stefan-Boltzmann constant

λ0

Heat conductivity of the water vapor at a given pressure

α

Energy accommodation coefficient for water vapor

tPriDry 

Primary drying time

ϵ

Porosity of the dried cake

τ

Tortuosity of the dried cake

r

Average radius of the pores in the dried cake

fast-DS

Fast design space

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Copyright information

© American Association of Pharmaceutical Scientists 2020

Authors and Affiliations

  • Feroz Jameel
    • 1
    Email author
  • Tong Zhu
    • 1
  • Ehab M. Moussa
    • 1
  • Brittney J. Mills
    • 1
  1. 1.Formulation Development, New Biological Entities, AbbVie (United States)North ChicagoUSA

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