Crystal engineering – nucleation, the key step

Davey, Roger J.; Allen, K.A.; Blagden, Nicholas; Cross, Wendy I.; Lieberman, H. F.; Quayle, Michael J.; Righini, S.; Seton, Linda; Tiddy, G. J. T.

doi:10.1039/b203521a

Cited by 195 publications

(194 citation statements)

References 33 publications

Supporting

Mentioning

183

Contrasting

Unclassified

Order By: Relevance

“…The controlled preparation and characterisation of crystal polymorphs, [1][2][3][4][5][6][7] that is, of different crystal forms of the same substance, is one of the major issues of modern crystal engineering and solid-state chemistry. [8][9][10][11][12][13][14] The reason for this interest stems from the fact that such studies can give fundamental information about molecular recognition, crystal nucleation, crystallisation, and the relationship between solid phases.…”

Section: Introductionmentioning

confidence: 99%

Hydrogen Bonding and Dynamic Behaviour in Crystals and Polymorphs of Dicarboxylic–Diamine Adducts: A Comparison between NMR Parameters and X‐ray Diffraction Studies

Gobetto

Nervi

Chierotti

et al. 2005

Chemistry A European J

View full text Add to dashboard Cite

Fumaric, malonic, maleic, and hydromuconic (HOOCCH2(CH)2CH2COOH) acids were used to prepare a series of hydrogen-bonded adducts or salts, depending on whether acid-base proton transfer takes place, with the dibase [N(muCH2CH2)3N] in various stoichiometric ratios. The resulting compounds have been investigated by using the 1H MAS, 15N, and 13C cross polarisation magic-angle spinning (CPMAS) methods and discussed in relation to X-ray diffraction studies to ascertain the nature of the O-HO, NH-O, and N+-HO- hydrogen bonds between the various species. In addition, two polymorphic forms of the malonic compound and a hydrate in the maleic case were examined. We also present the correlations between the chemical shifts of the hydrogen-bonded protons and those from the proton transfer reaction (acid-to-base) with the heavy atom distances. The dynamic behaviour in the solid-state of the [N(muCH2CH2)3N] adducts with fumaric 2:1, maleic 1:1 hydrate, and hydromuconic acids, and a malonate 2:1 polymorph adduct have been investigated by using variable-temperature 1H spin-lattice relaxation times. A substantial agreement between the activation energies obtained from fitting the T1 data and the results of potential energy barrier calculations demonstrates that the facile reorientation of the [N(muCH2CH2)3N] molecule occurs in several of the adducts.

show abstract

Section: Introductionmentioning

confidence: 99%

Hydrogen Bonding and Dynamic Behaviour in Crystals and Polymorphs of Dicarboxylic–Diamine Adducts: A Comparison between NMR Parameters and X‐ray Diffraction Studies

Gobetto

Nervi

Chierotti

et al. 2005

Chemistry A European J

View full text Add to dashboard Cite

show abstract

“…[1][2][3] In this communication we demonstrate the reproducible effect of solvents on the formation of isonicotinamide (INA) polymorphs. We establish that in solvents with strong hydrogen bond acceptors, the dominant configuration of the INA molecules with respect to each other is that of amide-pyridine heterosynthons (headto-tail chains) (Fig.…”

mentioning

confidence: 99%

Isonicotinamide self-association: the link between solvent and polymorph nucleation

et al. 2012

View full text Add to dashboard Cite

We show that, in a controlled and reproducible way, specific solvents lead to specific polymorphic forms of isonicotinamide. We argue on the basis of Raman and FTIR spectroscopy that the hydrogen bonding in solution kinetically drives the nucleation towards a specific form. This generally may lead to good understanding and control of polymorphism and crystal nucleation.The ability to control and predict crystal nucleation is of paramount importance from the viewpoint of crystal engineering, materials synthesis and crystalline product quality. [1][2][3] In this communication we demonstrate the reproducible effect of solvents on the formation of isonicotinamide (INA) polymorphs. We establish that in solvents with strong hydrogen bond acceptors, the dominant configuration of the INA molecules with respect to each other is that of amide-pyridine heterosynthons (headto-tail chains) (Fig. 1). Similarly, solvents with strong hydrogen bond donors lead to dominancy of amide-amide homosynthons (head-to-head dimers). This self-association in solution controls the polymorph nucleation of INA by controlling the building unit attaching to the nucleus.Polymorphism can be defined as the ability of a single chemical compound to form more than one crystal structure. 4 Polymorphism of active pharmaceutical ingredients is the subject of intense interest in both science and industry. 4,5 On the one hand, this is because crystalline product quality aspects such as drug efficacy, bioavailability and safety are affected by the polymorphic form present. On the other hand, polymorphs have economic and intellectual property implications.Often through empirical research, effects of solvent, supersaturation and impurities are observed on polymorph formation. 6 Recently, next to the two known forms of INA, 7 a third form was reported which incidentally and irreproducibly formed during a co-crystal screen from a multicomponent solution. 8 More recently, the difficult to control evaporative crystallization process yielded two new forms of INA.9 Form IV was obtained only as a mixture together with form II and/or V. For form V yields were often poor, typically 10%, and in some cases it could not be obtained.The crystal nucleation of INA is a most interesting process because of the strongly differing packing of form II and the other forms (ESIw). Isonicotinamide form II has been reported to be the most stable form at room temperature. 8 In the structure of form II the amide groups form homosynthons (dimers), 8 which in turn are hydrogen bonded through the oxygen atom and the remaining hydrogen of the amide group. Interestingly, the pyridine group does not participate in hydrogen bonding in the crystal structure of form II, contrary to all other currently known forms of INA. These consist of differently packed head-to-tail chains connected through heterosynthons of the amide and the pyridine group.The classical view of crystal nucleation is that building units attach to and detach from clusters of molecules.10 This attaching building unit could be...

show abstract

“…A temperatura e a supersaturação são considerados os parâmetros básicos de controle. 124 A primeira etapa da cristalização a partir de solução envolve a separação de fases, ou o nascimento de um novo cristal, e a segunda, o crescimento dos cristais. Estas duas etapas são conhecidas como nucleação e crescimento, respectivamente 125 e são determinantes na natureza do polimorfo que cristaliza.…”

Section: Preparação De Formas Cristalinasunclassified

Solid State in the Pharmaceutical Industry: A Brief Review

Prado¹,

Rocha²

2015

Revista Virtual De Química

View full text Add to dashboard Cite

Abstract:Most marketed pharmaceuticals consist of molecular crystals due to reasons of stability and ease handling during the development. Pharmaceutical solids can exist in the different forms. The arrangement of the molecules in a crystal determines its physical properties, influences the formulation, as well as dissolution rate and stability. Several examples are reported to demonstrate the importance of polymorphism in properties that can change the quality of the final product. A thorough understanding of the relationships between physical structures and the properties of pharmaceutical solids is therefore important in selecting the most suitable form. In this review, the different crystal forms of pharmaceuticals, the commonly used solid-state analytical techniques and advantages and disadvantages of each technique are discussed. In more detail, here is exposed the impact of solid forms in a galenic level.Keywords: Polymorphism; drug; analytical techniques; bioavailability; stability; processability. ResumoMuitos fármacos comercializados consistem em cristais moleculares devido a razões de estabilidade e para facilitar o manuseio durante o desenvolvimento. Sólidos farmacêuticos podem existir em diferentes formas. O arranjo das moléculas no cristal determina as suas propriedades físicas, influencia a formulação, assim como a taxa de dissolução e estabilidade. Diversos exemplos são relatados para demonstrar a importância do impacto do polimorfismo em propriedades que podem alterar a qualidade do produto final. Uma compreensão completa das relações entre as estruturas físicas e as propriedades dos sólidos farmacêuticos é, portanto, importante na escolha da forma mais apropriada. Nesta revisão, as diferentes formas cristalinas de fármacos, as técnicas de análise de estado sólido comumente utilizadas e as vantagens e desvantagens de cada técnica são discutidas. De forma mais detalhada é exposto o impacto das formas sólidas em nível galênico.

show abstract

Crystal engineering – nucleation, the key step

Cited by 195 publications

References 33 publications

Hydrogen Bonding and Dynamic Behaviour in Crystals and Polymorphs of Dicarboxylic–Diamine Adducts: A Comparison between NMR Parameters and X‐ray Diffraction Studies

Hydrogen Bonding and Dynamic Behaviour in Crystals and Polymorphs of Dicarboxylic–Diamine Adducts: A Comparison between NMR Parameters and X‐ray Diffraction Studies

Isonicotinamide self-association: the link between solvent and polymorph nucleation

Solid State in the Pharmaceutical Industry: A Brief Review

Contact Info

Product

Resources

About