Drug polymorphism: a review

Published on Jun 10, 2010in International Journal of Health Research
路 DOI :10.4314/IJHR.V2I4.55423
Maria Saifee5
Estimated H-index: 5
,
N Inamda1
Estimated H-index: 1
+ 1 AuthorsAmit A Rathi4
Estimated H-index: 4
Sources
Abstract
Formulators are charged with the responsibility of formulating a product which is physically and chemically stable, and bioavailable. Solid-state properties including polymorphism, solvate and salt formation can have a profound impact on important properties (solubility & stability) that are essential for successful development of drug candidates. Crystallization of pharmaceutically active ingredients, particularly those that possess multiple polymorphic forms, are among the most critical and least understood pharmaceutical manufacturing processes. Many process and product failures can be traced to a poor understanding and control of crystallization processes. Most drugs exhibits structural polymorphism and it is desirable to develop the most thermodynamically stable polymorph of the drug to assure reproducible bioavailability of the product over its shelf-life under a variety of real world storage conditions. There are occasional situations in which development of a meta-stable crystalline or amorphous form is justified to achieve the desired medical benefit. Such situation includes those in which faster dissolution rates or higher concentrations are desired in order to achieve rapid absorption and the efficiency or to achieve acceptable systemic exposure for low solubility drugs. This article briefly reviews the basic principle of polymorphism, different classes of phase transformations, the underlying transformation mechanisms with respective kinetic factors and hence the impact of polymorphism on pharmaceutical formulations. Keywords: Bioavailability, Crystallization, Polymorphism.
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References62
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Source
Formulators are charged with the responsibility to formulate a product which is physically and chemically stable, manufacturable, and bioavailable. Most drugs exhibit structural polymorphism, and it is preferable to develop the most thermodynamically stable polymorph of the drug to assure reproducible bioavailability of the product over its shelf life under a variety of real-world storage conditions. There are occasional situations in which the development of a metastable crystalline or amorphou...
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Source
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Source
#2David E. BugayH-Index: 11
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#1Nicholas Blagden (University of Manchester)H-Index: 26
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#1Kenneth Craig Waterman (Pfizer)H-Index: 15
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