Identification, Preparation, and Characterization of Several Polymorphs and Solvates of Terazosin Hydrochloride

Bauer, John F.; Morley, James A.; Spanton, Stephen G.; Leusen, F. J. J.; Henry, Rodger F.; Hollis, S.; Heitmann, W.; Mannino, A.; Quick, John; Dziki, Walter

doi:10.1002/jps.20425

Cited by 18 publications

(52 citation statements)

References 27 publications

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“…Sensitive analytical methods such as differential scanning calorimetry, powder X-ray diffraction, Fourier transform infrared spectroscopy and scanning electron microscopy have been used to characterize the various forms (11)(12)(13)(14)(15)(16)(17). Above all, much attention has been paid to utilization of the solution calorimeter, which generates data by dissolving a solid compound into a solvent, providing the enthalpy of solution which is a direct reflection of its lattice energy.…”

mentioning

confidence: 99%

Characterization of solvatomorphs of methotrexate using thermoanalytical and other techniques

Chadha¹,

Arora²,

Kaur³

et al. 2009

Acta Pharmaceutica

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Investigation of polymorphism and solvatomorphism in drug molecules is an important step in any pre-formulation program from both biopharmaceutical and technological point of view (1, 2). It is well known that polymorphs are different crystalline forms of the same compound whereas the inclusion of a solvent in a crystal lattice gives rise to pseudopolymorphs or solvatomorphs (2). One of the most relevant features among polymorphic modifications is the difference in their solubility and dissolution rate that affect their bioavailability (3-5).In crystal hydrates/solvates, the combination of intermolecular forces (hydrogen bonding) and crystal packing can produce very strong solvent-solid interactions leading to completely new properties in the solid state (6, 7). Some stable solvatomorphs require vigorous conditions for desolvation before melting, while others lose the solvent of crys- Identification and characterization of different forms of methotrexate were carried out by crystallization from different solvents. Five different forms of the drug were obtained. Appearance of a desolvation endotherm in the DSC accompanied by mass loss in TGA for forms I, II, IV and V showed these forms to be acetonitrile solvate hydrate (form I), trihydrate (forms II and IV) and dimethylformamide solvate (form V), respectively. However, the desolvation peak was absent in form III (obtained from methanol) indicating the absence of any solvent of crystallization. This form was found to be partially crystalline by its XRPD pattern. Solution calorimetry was further used to differentiate between the forms as they differ in lattice energy, resulting in different enthalpies of solution. The dissolution and solubility profiles were correlated with the enthalpy of solution and subsequently with crystallinity of all the forms; the least endothermic form (form III) had the highest dissolution rate.

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mentioning

confidence: 99%

Characterization of solvatomorphs of methotrexate using thermoanalytical and other techniques

Chadha¹,

Arora²,

Kaur³

et al. 2009

Acta Pharmaceutica

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“…The atomic radius of the chlorine anion was increased from the default 3.95 Å to 4.10 Å . 116 This modified force field was certainly not accurate enough to predict the crystal structures of terazosin hydrochloride from first principles, but it was good enough to generate crystal packing alternatives which could be used together with the experimental powder diffraction patterns to identify the crystal structures of the two anhydrous forms that had not yet been solved.…”

Section: Terazosin Hydrochloridementioning

confidence: 99%

“…In addition to the methanol solvate, a dihydrate has also been found. 116 These forms all exist at room temperature and their relative stabilities have been determined experimentally.…”

Section: Terazosin Hydrochloridementioning

confidence: 99%

“…However, low quality X-ray powder diffraction patterns were available and a crystal structure prediction study was carried out to generate possible crystal structures for these two anhydrous forms. 116 Terazosin hydrochloride is a real challenge for crystal structure prediction because the cation is large and flexible and because its ionic nature complicates the calculation of the electrostatic contribution to the lattice energy. However, knowledge of the experimental crystal structures of four forms was used to deduce the most likely conformation of the cation as well as the protonation site and the most likely location of the chlorine anion.…”

Section: Terazosin Hydrochloridementioning

confidence: 99%

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Polymorph Prediction of Small Organic Molecules, Co-crystals and Salts

Leusen

Kendrick

2011

Pharmaceutical Salts and Co-Crystals

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Crystal structure prediction is regarded by some as the holy grail of crystal engineering because reliable and accurate prediction of the polymorphs that a compound can crystallise in would allow the design of organic materials with specific properties from first principles. This contribution provides an overview of the current status of crystal structure prediction of small organic molecules in general and focuses on the specific issues encountered in the prediction of co-crystal and salt structures. Both the global optimisation problem of searching for all possible crystal structures of a compound and the problem of calculating accurate lattice energies in order to rank potential crystal structures according to stability are discussed. A number of illustrative examples are presented, including an overview of the Cambridge Crystallographic Data Centre's blind tests in crystal structure prediction, as well as some examples of co-crystals, solvates and salts.

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“…62 The rich solid-state chemistry associated with terazosin hydrochloride has been discussed, with four nonsolvated polymorphs, a methanol solvate and its desolvate, and a dihydrate all being reported. 63 The dihydrate was found to be the most stable crystal form under aqueous conditions, while Form-II was found to be the most stable of the nonsolvated polymorphs. Two polymorphs of buspirone hydrochloride were characterized by a full range of techniques, with the two forms being found to constitute an enantiotropic pair.…”

Section: Polymorphic Systemsmentioning

confidence: 99%

Polymorphism and Solvatomorphism 2006

Brittain¹

2008

Journal of Pharmaceutical Sciences

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Identification, Preparation, and Characterization of Several Polymorphs and Solvates of Terazosin Hydrochloride

Cited by 18 publications

References 27 publications

Characterization of solvatomorphs of methotrexate using thermoanalytical and other techniques

Characterization of solvatomorphs of methotrexate using thermoanalytical and other techniques

Polymorph Prediction of Small Organic Molecules, Co-crystals and Salts

Polymorphism and Solvatomorphism 2006

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