Structural Study of Polymorphs and Solvates of Finasteride

Othman, Abdullah; Evans, John S. O.; Evans, Ivana Radosavljević; Harris, Robin K.; Hodgkinson, Paul

doi:10.1002/jps.20940

Cited by 67 publications

(93 citation statements)

References 28 publications

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“…Thus, form I is an acetonitrile solvate hydrate. The existence of a mixed solvate with a single desolvation peak has also been reported in the literature (15).…”

Section: Dsc and Tg Analysissupporting

confidence: 56%

“…Also, the position of the peak corresponding to 100 % intensity was different; it was located at 2q of 26.92 o in the commercial sample, at 2q of 9.41 o in form II, at 2q of 27.01 o in form IV. The deviation in the relative intensity might be accounted for by some preferred orientation in the sample (15). The XRPD pattern for forms I and V was definitely different, showing that they crystallized in a distinctly different arrangement.…”

Section: Xrpdmentioning

confidence: 96%

“…1f) obtained from DMF and water showed a desolvation endotherm at 120°C with mass loss of 16.50 % (calculated 16.79 %), showing form V to be a mixed solvate of DMF and water with the stoichiometry of 1:1:1 (15).…”

Section: Dsc and Tg Analysismentioning

confidence: 98%

“…The binding strength for water and solvents (15,16,23) was also calculated for all the forms (Table I) Table I shows that water molecules are not tightly bound in the crystals of methotrexate. However, stronger interaction with methotrexate host is noted for DMF and acetonitrile.…”

Section: Dsc and Tg Analysismentioning

confidence: 99%

“…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%

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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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“…Thus, form I is an acetonitrile solvate hydrate. The existence of a mixed solvate with a single desolvation peak has also been reported in the literature (15).…”

Section: Dsc and Tg Analysissupporting

confidence: 56%

Section: Xrpdmentioning

confidence: 96%

Section: Dsc and Tg Analysismentioning

confidence: 98%

Section: Dsc and Tg Analysismentioning

confidence: 99%

mentioning

confidence: 99%

See 3 more Smart Citations

Characterization of solvatomorphs of methotrexate using thermoanalytical and other techniques

Chadha¹,

Arora²,

Kaur³

et al. 2009

Acta Pharmaceutica

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Crystallography and NMR: An Overview

Harris

2008

Encyclopedia of Magnetic Resonance

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Advances in technology are rendering some of these difficulties less restrictive. In addition, in recent years, the power of powder diffraction techniques has been greatly increased so that it is feasible in many cases to obtain detailed crystal structures by this means. 9 This is particularly valuable, for example, for samples of small crystals embedded in an amorphous matrix, as is the case for many ceramic systems. Other advances in X-ray diffraction procedures allow electron

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