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  • Title: Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates.
    Author: Blagden N, de Matas M, Gavan PT, York P.
    Journal: Adv Drug Deliv Rev; 2007 Jul 30; 59(7):617-30. PubMed ID: 17597252.
    Abstract:
    The increasing prevalence of poorly soluble drugs in development provides notable risk of new products demonstrating low and erratic bioavailability with consequences for safety and efficacy, particularly for drugs delivered by the oral route of administration. Although numerous strategies exist for enhancing the bioavailability of drugs with low aqueous solubility, the success of these approaches is not yet able to be guaranteed and is greatly dependent on the physical and chemical nature of the molecules being developed. Crystal engineering offers a number of routes to improved solubility and dissolution rate, which can be adopted through an in-depth knowledge of crystallisation processes and the molecular properties of active pharmaceutical ingredients. This article covers the concept and theory of crystal engineering and discusses the potential benefits, disadvantages and methods of preparation of co-crystals, metastable polymorphs, high-energy amorphous forms and ultrafine particles. Also considered within this review is the influence of crystallisation conditions on crystal habit and particle morphology with potential implications for dissolution and oral absorption.
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