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Applications of Freezing and Freeze-Drying in Pharmaceutical Formulations

  • Ken-ichi Izutsu
Chapter
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 1081)

Abstract

Freeze-drying is a popular method to prepare pharmaceutical formulations containing structurally complex active ingredients and drug delivery system carriers. The solidification performed at lower temperature significantly improves storage stability of proteins, peptides, antibiotics, vaccines, and liposomes, which are marginally stable in aqueous solutions. Individual components of the freeze-drying process (freezing, primary drying, secondary drying), however, expose proteins to various stresses. Certain excipients, including disaccharides (e.g., sucrose, trehalose) and amino acids, can be added to protect the proteins and supramolecular drug delivery systems against physical stress associated with freezing and storage by substituting the molecular interactions provided by water molecules. Some excipients embed the active ingredients in glass-state solids with low molecular mobility, thereby reducing chemical reactivity. Thus, the use of appropriate excipients and process control is important to protect proteins during freeze-drying. This chapter describes the applications of freeze-drying in the pharmaceutical production process, mainly focusing on formulation and process optimization for protein therapeutics.

Keywords

Pharmaceutical formulations Freeze-drying Protein Stabilization Excipient 

Abbreviations

ADC

Antibody–drug conjugate

API

Active pharmaceutical ingredient

BSE

Bovine spongiform encephalopathy

CJD

Creutzfeldt-Jakob disease

DDS

Drug delivery system

DSC

Differential scanning calorimeter

LiCl

Lithium chloride

MS

Mass spectrometry

NaCl

Sodium chloride

OD

Orally disintegrating

PAT

Process analytical technology

PVP

Polyvinylpyrrolidone

Tg

Glass transition temperature

Tg′

Glass transition temperature of maximally freeze-concentrated solute

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Copyright information

© Springer Nature Singapore Pte Ltd. 2018

Authors and Affiliations

  1. 1.National Institute of Health SciencesKawasakiJapan

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