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A Package of Established Analytical Tools to Investigate the Solid-State Alteration of Lipid-Based Excipients

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Solid state amorphization of pharmaceuticals.

J F Willart¹, M Descamps

¹Laboratoire de Dynamique et Structure des Matériaux Moléculaires, UMR CNRS 8024, ERT 1066, Université de Lille 1, Bât. P5, 59655 Villeneuve d'Ascq, France.

Molecular Pharmaceutics

|October 29, 2008

Summary

This summary is machine-generated.

This review explores nonconventional methods for creating amorphous solids, such as milling and dehydration, and discusses their stability and properties. It examines factors influencing crystal-to-glass transformations and rationalizes these processes using nonequilibrium physics concepts.

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Area of Science:

Solid-state chemistry
Materials science
Physical chemistry

Background:

Amorphous solids are typically formed by liquid supercooling or solute concentration.
Pharmaceutical processes can induce crystal-to-amorphous transformations with stability implications.

Purpose of the Study:

Illustrate diverse routes to amorphize compounds (supercooling, dehydration, milling, annealing).
Examine factors favoring crystal-to-glass over crystal-to-crystal transformations.
Discuss amorphous intermediates in milling-induced solid-solid conversions.
Address chemical stability during solid-state amorphization.
Characterize amorphous states from nonconventional routes.
Analyze milling conditions' effects on glass properties.
Rationalize transformations using nonequilibrium physics concepts like effective temperature.

Main Methods:

Review of literature on solid-state amorphization techniques.
Analysis of factors influencing phase transformations.
Discussion of chemical stability and amorphous state characterization.
Application of nonequilibrium physics principles.

Main Results:

Multiple nonconventional routes can yield amorphous solids.
Factors influencing crystal-to-glass transitions are identified.
Amorphous intermediates play a role in solid-state milling.
Chemical stability and properties of amorphous solids depend on formation route and conditions.

Conclusions:

Nonconventional amorphization methods offer alternatives to traditional techniques.
Understanding transformation pathways and amorphous state properties is crucial for pharmaceutical applications.
Nonequilibrium physics provides a framework for rationalizing these solid-state transformations.