Analysis of organic polymorphs. A review

Threlfall, Terry L.

doi:10.1039/an9952002435

Cited by 528 publications

(394 citation statements)

References 201 publications

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“…So a collection of crystals will start with a range of stabilities, but as the sizes and the imperfections are gradually ironed out, the measured solubility will approach the thermodynamic value. This sequence is probably a further 35 reason why the exact measurement of solubility is so difficult and time-consuming 33 . The observations of Malivuk et al 34 on the dissolution and growth of crystals at concentrations respectively greater and less than the thermodynamic solubility value support what is being described here.…”

Section: The Dead Zonementioning

confidence: 99%

A perspective on the growth-only zone, the secondary nucleation threshold and crystal size distribution in solution crystallisation

Threlfall

Coles

2016

CrystEngComm

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The metastable zone between the solubility curve and the crystallisation curve can be divided into two regions, separated by the secondary nucleation threshold. At a supersaturation less than that of the secondary nucleation threshold seeds will grow but not proliferate. At greater supersaturations, they will proliferate. Although this concept has been known in connection with the commercial crystallisation of sucrose and of lactose for almost a century it is virtually unrecognised beyond the sugar and dairy 10 industries. The consequences are explored of the existence of such a boundary on the crystallisation process and the influence on crystal size distribution. It is recognised that the secondary nucleation threshold is the 'seeded metastable limit', but there are important consequences of avoiding the latter term. Mullin's 'Latent Period' is shown to be closely related to the 'growth only' zone within the metastable zone.15

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Section: The Dead Zonementioning

confidence: 99%

A perspective on the growth-only zone, the secondary nucleation threshold and crystal size distribution in solution crystallisation

Threlfall

Coles

2016

CrystEngComm

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“…Over the last several decades, there has been a sharp rise in the interest in polymorphic systems, especially in pharmaceuticals. [1][2][3] These polymorphs can lead to the different physiochemical properties of the material. For example, different polymorphs may have different rates of dissolution or bioavailability, and may even affect the stability of the drug.…”

Section: Introductionmentioning

confidence: 99%

Polymorphic Forms of Furosemide Characterized by THz Time Domain Spectroscopy

Min¹,

Ma²,

Wang³

2009

Bulletin of the Korean Chemical Society

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Terahertz time domain spectroscopy (THz-TDS) is applied in transmission to identify the five forms of modifications of furosemide and one commercial product from 0.3 THz to 1.6 THz at room temperature. The different absorption spectra of the different forms are sensitive to crystal structures. Density function theory (DFT) calculation was used to understand the vibrational modes of furosemide in the THz region. X-ray powder diffractometry (XRPD) was applied to confirm the different forms of modifications. The results demonstrate that THz-TDS is a potential analytical technique in investigating polymorphic forms in the pharmaceutical fields.

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“…In the processing of crystalline organic fine chemicals and pharmaceuticals, crystal polymorphism is of tremendous importance; a large proportion of all organic compounds exhibit polymorphism, and different solid forms of a substance display different solid state properties, e.g. stability, crystal shape, compressibility, density and dissolution rate, leading to differences in handling and processing properties of the compound, and in the shelf life and bioavailability of drugs 5 . It is of the greatest importance to the pharmaceutical and fine chemical industry to ensure reliable and robust processes, and conformity with Good Manufacturing Practice, and thus one regulatory requirement for active pharmaceutical ingredients is the identification of possible polymorphic forms.…”

Section: Introductionmentioning

confidence: 99%

Force Fields and Point Charges for Crystal Structure Modeling

Svärd

Rasmuson

2009

Ind. Eng. Chem. Res.

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ABSTRACT. Molecular simulation is increasingly used by chemical engineers and industrial chemists in process and product development. In particular, the possibility to predict the structure and stability of potential polymorphs of a substance is of tremendous interest to the pharmaceutical and specialty chemicals industry. Molecular mechanics modelling relies on the use of parameterized force fields and methods of assigning point charges to the atoms in the molecules. In commercial molecular simulation software a wide variety of such combinations are available, and there is a need for critical assessment of the capabilities of the different alternatives.In the present work, the performance of several molecular mechanics force fields combined with different methods for the assignment of atomic point charges have been examined with regard to their ability to calculate absolute crystal lattice energies and their capacity to identify the experimental structure as a minimum on the potential energy hypersurface. Seven small, aromatic mono-molecular crystalline compounds are used in the evaluation. It is found that the majority of the examined methods cannot be used to reliably predict absolute lattice energies. The most promising results were obtained with the Pcff force field using integral charges, and the Dreiding force field using Gasteiger charges, both of which performed with an accuracy of the same order of magnitude as the variations in experimental lattice energies. Overall, it has been observed that the best results are achieved if the same force field method is used to relax the crystal structure and calculate the energy, and to optimize and calculate the energy of the gas phase molecule used for the correction for changes in molecular geometry. The Pcff and Compass force fields with integral charges have been found to predict relaxed structures closest to the experimental ones.In addition, five different methods for determining point charges fitted to the electrostatic potential (ESP-charges), available in the same software, have been evaluated. For each method, the molecular geometries of ten small, organic molecules were optimized, and ESP-charges calculated and analyzed for linear correlation with a set of reference charges of an accepted standard method, HF/6-31G*. Dmol-3 gives charges that correlate well with the reference charge.The charges from Vamp are not linearly scalable to the HF/6-31G*-level, which is attributed partly to the geometry optimization but mainly to the calculation of the ESP and the subsequent charge fit.

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Analysis of organic polymorphs. A review

Cited by 528 publications

References 201 publications

A perspective on the growth-only zone, the secondary nucleation threshold and crystal size distribution in solution crystallisation

A perspective on the growth-only zone, the secondary nucleation threshold and crystal size distribution in solution crystallisation

Polymorphic Forms of Furosemide Characterized by THz Time Domain Spectroscopy

Force Fields and Point Charges for Crystal Structure Modeling

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