Polymorphism and Solvatomorphism 2006

Brittain, Harry G.

doi:10.1002/jps.21274

Cited by 44 publications

(29 citation statements)

References 168 publications

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“…The tendency of pharmaceutical solids to crystallize in multiple crystal forms and the significance of this phenomenon has been well demonstrated during this decade and is a subject of fundamental, practical and legal interest (1)(2)(3)(4)(5). Various forms may appear during the crystallization process, depending upon the factors such as solvent, temperature, additives and preparation methods.…”

Section: Introductionmentioning

confidence: 99%

An Insight into Thermodynamic Relationship Between Polymorphic Forms of Efavirenz

Chadha

Arora²,

Saini³

et al. 2012

J Pharm Pharm Sci

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-Purpose:The aim of the work is to study the crystallization of efavirenz to understand the preferential formation of various polymorphic forms, to establish their identity, to study the transformation between the polymorphic forms on heating and to determine their free energy. Methods: Slow crystallization from different solvents under controlled conditions was employed to prepare various crystalline forms. The TGA and DSC were used to study their thermal behavior and inter-conversion of these forms. The calorimetrically determined enthalpies of solution and solubility data are utilized to determine the transition temperatures. Results: Six polymorphic forms of efavirenz are identified and characterized completely. The TGA scans of all the forms did not show any mass loss indicating absence of hydrate or solvate. The thermally induced transformations are observed in the DSC scans of five forms II-VI indicating them to be metastable which are converted to stable higher melting forms. The melting temperature and enthalpy of fusion of lower melting (Form L ) and higher melting forms (Form H ) reveal that four of these polymorphic pairs are monotropically related. The enthalpies of solution of Form L are found to be more exothermic as compared to corresponding Form H . The transition temperature (T t ) determined using enthalpy of solution and solubility data was found to be higher than the melting of both the forms except for polymorphic pair VI L /VI H . The effect of ΔC p on transition temperature is also reported. Conclusions: The form I is found to be thermodymanically most stable but least soluble. The forms II-V are metastable and are converted irreversibly to stable forms. The enthalpy of fusion rule and virtual transition temperature provided complementary evidence for the existence of monotropy in these polymorphic pairs. However, enantiotropy is demonstrated in VI L /VL H pair and is well established in our study. Novelty: The present study reveals the thermodynamic aspects of various isolated polymorphic forms of efavirenz. Solution calorimetry along with other techniques is used to study the transformation of one form to another. The emphasis is laid on determination of transition temperature of various polymorphic pairs which has not been reported earlier.

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Section: Introductionmentioning

confidence: 99%

An Insight into Thermodynamic Relationship Between Polymorphic Forms of Efavirenz

Chadha

Arora²,

Saini³

et al. 2012

J Pharm Pharm Sci

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“…Scientists' interest in understanding pharmaceutically relevant aspects of polymorphism have increased over the years, in particular the drugs' different metastable polymorphic forms, the polymorphic forms dissolution rate, and their thermodynamic properties, as well as the in vivo drug kinetics [1][2][3].…”

Section: Introductionmentioning

confidence: 99%

Quantifying Solid-State Mixtures of Crystalline Indomethacin by Raman Spectroscopy Comparison with Thermal Analysis

Atef

Chauhan

Prasad

et al. 2012

ISRN Chromatography

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This paper investigates Raman spectroscopy as a quick and reliable method to quantify the alpha (α) and gamma (γ) polymorphic forms of indomethacin compared to differential scanning calorimetry (DSC). Binary mixtures with different ratios of α and γ indomethacin were prepared and analyzed by Raman and DSC. The Raman method was found to be more reliable and superior compared to DSC. The partial conversion of the alpha to gamma polymorphic form during the DSC measurement was the major limitation for the use of full DSC as a quantitative method and resulted in difference between the calculated and measured enthalpy of both polymorphic forms.

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“…The Raman spectrum of the two polymorphs 5(1) and 5(2) are different in the C-H stretching region at ~3000 cm , and ~800 cm relevance in pharmaceutical polymorphism because typical drug molecules represent a confluence of conformational mobility and functional complexity [16,17].…”

Section: Raman Analysismentioning

confidence: 99%

Polymorphic behavior of an organic compound

Nithya

Ramasamy²,

Kanakam³

2017

Asian J Pharm Clin Res

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Objective: Polymorphic crystals were exhibited in many organic compounds. The frequency changes, relative intensities, band contours, and number of bands were observed in the spectra of different polymorphism which may be due to molecule-molecule interactions in the crystal unit cells. The shape of a molecule at its site in the unit cell is distorted by molecular interactions. Methods:The identification of a pure crystal form and to quantify a mixture of two forms infrared and Raman spectra of different crystalline forms of the same organic compound can be used. 2'-chloro-4-methoxy-3-nitro benzil (1) was synthesized and its two polymorphic forms were obtained by recrystallization from the solvents acetone/chloroform and ethanol. The polymorphism present in the compound was confirmed by single crystal X-ray crystallography and differential scanning calorimetry. Results:The polymorph 1.1 crystallizes as triclinic P-1 space group in the solvent acetone -chloroform and the polymorph 1.2 crystallizes as monoclinic P21/c space group in the solvent ethanol. Discussion:The intermolecular lattice energy and the interplay of molecular conformation in the crystallization and stability of polymorphs are identified by X-ray crystal structures of conformational polymorphs.

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Polymorphism and Solvatomorphism 2006

Cited by 44 publications

References 168 publications

An Insight into Thermodynamic Relationship Between Polymorphic Forms of Efavirenz

An Insight into Thermodynamic Relationship Between Polymorphic Forms of Efavirenz

Quantifying Solid-State Mixtures of Crystalline Indomethacin by Raman Spectroscopy Comparison with Thermal Analysis

Polymorphic behavior of an organic compound

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