Crystal engineering of active pharmaceutical ingredients to improve solubility and dissolution rates.

By N. Blagden, M. Matas, Pauline T. Gavan, P. York. Advanced Drug Delivery Reviews, 2007

1,438 citations recorded by the source corpus.

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.

Subfields: Materials Chemistry, Pharmaceutical Science, Physical and Theoretical Chemistry

View Paper: https://www.semanticscholar.org/paper/b7e9b9be2610d041cb11ac319c404beefc4b89a5

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In Materials Chemistry

In Pharmaceutical Science

Citations in the corpus

Drug Solubility: Importance and Enhancement Techniques (2012, background): “The process involves dissolving the drug in a solvent and precipitating it in a controlled manner to produce nanoparticles through addition of an antisolvent (usually, water) [58].”
Pharmaceutical particle technologies: An approach to improve drug solubility, dissolution and bioavailability (2014, methodology): “…new and emerging method of controlled crystallization that can be described as the ‘exploitation of noncovalent interactions between molecular or ionic components for the rational design of solid e state structures that might exhibit interesting electrical, magnetic, and optical properties ’ [43].”
Strategies to Address Low Drug Solubility in Discovery and Development (2013, background): “…engineering has also emerged (Biradha et al., 2011) to describe strategies that include not only deliberate manipulation of the crystal lattice but also manipulation of crystallization conditions to isolate drug crystals of a particular size and shape (Nokhodchi et al., 2003; Blagden et al., 2007).”
Formulation design for poorly water-soluble drugs based on biopharmaceutics classification system: basic approaches and practical applications. (2011, background): “Crystal modification (Blagden et al., 2007), particle size eduction (Xia et al.”