Jump to main content
US EPA
United States Environmental Protection Agency
Search
Search
Main menu
Environmental Topics
Laws & Regulations
About EPA
Health & Environmental Research Online (HERO)
Contact Us
Print
Feedback
Export to File
Search:
This record has one attached file:
Add More Files
Attach File(s):
Display Name for File*:
Save
Citation
Tags
HERO ID
5078536
Reference Type
Journal Article
Title
Freeze-drying from organic co-solvent systems, part 2: process modifications to reduce residual solvent levels and improve product quality attributes
Author(s)
Kunz, C; Schuldt-Lieb, S; Gieseler, H
Year
2019
Is Peer Reviewed?
Yes
Journal
Journal of Pharmaceutical Sciences
ISSN:
0022-3549
EISSN:
1520-6017
Volume
108
Issue
1
Page Numbers
399-415
Language
English
PMID
30017885
DOI
10.1016/j.xphs.2018.07.002
Web of Science Id
WOS:000456898100059
Abstract
The use of co-solvent systems can benefit the freeze-drying process and product performance. In this study, cycle designs were applied based on existing recommendations for water-based formulations. Modifications thereof and the influence on the process (e.g., drying times) and product quality attributes (e.g., product appearance, residual solvent) were tested for various cosolvent systems. It was found that fast freezing was associated with the formation of large crystals for 50 mg/g polyvinylpyrrolidone in 40% 1,4-dioxane (w/w), resulting in a 7% reduction of primary drying. The application of high shelf temperatures during primary drying for 50 mg/g polyvinylpyrrolidone in 70% tert-butanol was feasible, resulting in shorter primary drying times but high residual solvent levels (7.7%). Most notable was that the inclusion of an evaporation step after freezing improved the product appearance for low-melting co-solvents (10% ethanol and 10% acetone). No ice or solvent nucleation occurred in the case of 50 mg/g mannitol in 50% N,N-dimethylacetamide during the normal freezing stage. Instead, the solution viscosity significantly increased after cooling to low shelf temperatures, followed by product evaporation (rather than sublimation) during the drying phase and failure to form a product cake after drying. The application of annealing enabled nucleation and sublimation.
Keywords
freeze-drying/lyophilization; calorimetry (DSC); X-ray powder diffraction; organic solvents; residual solvent
Tags
IRIS
•
tert-Butanol
Excluded/ Not on Topic
Methodology/Solvent
LitSearch: Jan 2017 - July 2019
PubMed
OPPT REs
•
OPPT_1,4-Dioxane_D. Exposure
Total – title/abstract screening
Supplemental Search
Consumer Use
Home
Learn about HERO
Using HERO
Search HERO
Projects in HERO
Risk Assessment
Transparency & Integrity