文档介绍：REGULATORY SCIENCE OF LIPOSOME DRUG PRODUCTS
Diane J. Burgess, .
Professor of Pharmaceutics
University of Connecticut
Office of Testing and Research
CDER, FDA
Burgess, June 28, 2001
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Outline
What are liposomes?
What are they used for?
What drugs?
Why liposomes?
Liposome formulation
Liposome characterization
Safety concerns
Performance concerns
In vitro release testing
stability
Burgess, June 28, 2001
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Outline Continued
Purpose of in vitro release tests?
Design of in vitro release test
Accelerated/stress tests
Method variables affecting release
Methods under development
In vivo factors affecting release
In vivo data and models?
IVIVC?
Research proposal
Burgess, June 28, 2001
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LIPOSOMES
Liposomes are colloidal, lipid vesicles consisting of one or more self-assembled lipid bilayers enclosing a similar number of partments.
Lipids, such as lecithin (diacylphosphatidylcholine), are amphiphilic molecules. Due to the bulky nonpolar part of the molecule they do not pack into spherical micelles in aqueous phase but rather self-assemble into bilayers which tend to self-close at low concentrations into spherical structures.
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LIPOSOMES Contd.
Liposomes can be subcategorized into:
Small unilamellar vesicles (SUV), 25 to 100 nm in size that consist of a single lipid bilayer
Large unilamellar vesicles (LUV), 100 to 400 nm in size that consist of a single lipid bilayer
Multilamellar vesicles (MLV), 200 nm to several microns, that consist of two or more concentric bilayers
Vesicles above 1 μm are known as giant vesicles.
Burgess, June 28, 2001
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Liposomes
Localized and rate controlled delivery:
Improved therapeutic response
Achieve appropriate tissue or blood levels
Reduced adverse reactions
Less drug administered
Targeted drug release
Lower dosing frequency
Improved pliance
Simpler dosing regimens
Lower cost per dose
Utilization of otherwise un-pounds
Poorly soluble drugs
Burgess, June 28, 2001
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Drug Candidate S