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Characterization of Polymorphic Forms (Polymorphism)

Polymorphism Analysis / Polymorphism Testing

Polymorphism is derived from Greek word ‘poly’ means many and ‘morphs’ mean shape. Polymorphism is defined as ability of a molecule (Solid material) to exhibit more than one crystalline from (Crystal structure).

Crystalline forms have different conformations of the molecules in the crystal lattice. Amorphous forms consist of disordered arrangement of molecules that do not possess a distinguishable crystal lattice.

Solvates are crystal forms containing either stoichiometric or non-stoichiometric amounts of a solvent. If the incorporated solvent is water, the solvates are commonly known as Hydrates.

Polymorphism play an important role in chemical research, where complete characterization of a material has vital role in applications of foods, Pharmaceuticals & fine chemicals, dye stuffs, pigments, agrochemicals, polymer and explosives.

Polymorphic form exists in different crystalline shapes, the common crystals structures are given below-

  1. Cubic
  2. Hexagonal
  3. Tetragonal
  4. Orthorhombic
  5. Monoclinic and
  6. Triclinic
Polymorphic Characterization (Polymorphism)

Characterization of Polymorphism

NRPL adopts various methods to characterize Polymorphic forms of a given sample. Which includes, Thermal    analysis like DSC (Differential scanning calorimeter), DTA (Differential thermal analysis), TGA (Thermo        gravimetrical analysis), Spectroscopic techniques like FTIR (Fourier-transform infrared spectroscopy) and          powder XRD (X-ray powder diffraction) and single crystal XRD.

Thermal properties of polymorphs are important features to characterize the polymorph, which can be obtained by applications of instrumental techniques like DSC/DTA ad TGA. They generally give a valuable data like Melting points (MP), Glass transitions temperature (TG) and energy taken during MP & TG.

FTIR give valuable information of functional groups present in given sample along with data of changes in frequencies, relative intensities, bad contours, and number of bands. Differences in spectra of FTIR are attributed to internal molecular arrangement in crystal.

Raman spectra offers more information related to chemical attributes of polymorphism where as DSC, TGA & XRD offer physical attributes in Raman spectroscopy chemical structure is evaluated by detecting scattering light at low wave numbers derive from crystal lattice vibration, y laser irradiation of the sample. We cannot get much information of amorphous sample using DSC & XRD whereas Raman spectroscopy can be used to evaluate crystal and amorphous structures. As it is difficult to measures samples with less reflection (less diffraction) such as amorphous an minute crystals using X-ray crystal analysis as sample includes a mixture of crystal and amorphous in this regard Raman spectra is more effective.

Raman spectra, FTIR & XRD are non-destructive analytical techniques, while thermal techniques are destructive. XRD is most widely used reliable analytical technique for characterization of various crystal forms. Through different patterns changes in spectral patterns of XRD such as peak shouldering, new peak (or) a shift in peak is ascribed to polymorphic transitions. Novel techniques like solid state NMR is used to evaluate morphological characteristics of crystal lattice changes as a function of various parameters such as Temperature, Nature of solvent, Rate of precipitation, Conditions of crystallization, inter conversion between solid forms (from solvate to un-solvate & vice versa) absorption and release of vapor pressure, pressure and mechanical treatment etc. Techniques like those that hot stage microscopy, DSC & micro-DSC scan be adopted to obtain an semi empirical energy-temperature diagram, that can be helpful in designing protocols for screening for crystal forms.

Apart from these traditional techniques for evaluating new crystal forms various other methods are used and developed in search for multiple crystal forms. These methods are base on established traditional knowledge reported in literature and application of crystal engineering principles (Based on hydrogen bonding patterns) for new multi component solids.

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