Polymorphism: Its application in the development of pharmaceutical dosage form
Polymorphism comes from the Greek words, Polus = many and morph = shape. Polymorphism means existence of substance in more than one form. Many pharmaceutical solids can exist in different physical forms. Polymorphism is often characterized as the ability of a drug substance to exist as two or more crystalline phases that have different arrangements and/or conformations of the molecules in the crystal lattice. However, they share one common form once they are in solution form. Polymorphism is very important in those areas of chemical research where full characterization of a material has a pivotal role in ...view middle of the document...
* Optical microscopy: It determines the optical properties (birefringence, indices of refraction, interference figure, dispersion color etc) and morphological properties of particles.
* Scanning Electron Microscopy: It determines surface topography and type of crystals (Polymorphism and crystal habit)
* Hot Stage Microscopy: The polarizing microscope fitted with a hot stage or cold stage is an extremely valuable tool for the characterization of polymorphic or solvate system.
* Single Crystal X-ray Diffraction: Single crystal X – ray diffraction provides the most complete information about the solid state. It will give information about the position of molecular groups within the crystal and thus actually defines the differences between the different forms.
* Powder X – Ray Diffraction: Crystalline materials in powder form give characteristic X – ray diffraction patterns made up of peaks in certain position and varying intensities.
* Differential Scanning Calorimetric (DSC): It measures the heat loss or gain resulting from physical or chemical changes within a sample
* Differential Thermal Analysis (DTA): It monitors the difference in temperature existing between a sample and a reference as a function of temperature. It is useful in fusion, boiling, sublimation, vaporization; crystalline structure inversion, solid-solid transition, and water loss generally produce endothermic effects, and exothermic effects.
* Thermo gravimetric analysis (TGA): It is a technique that measures changes in weight that occur to a sample as function of temperature over time.
* Fourier Transforms Infrared Spectroscopy (FT-IR): It is the identification of the drug present and distinguishing between solvates and anhydrous form then for identifying polymorphs.
* Raman Spectroscopy: It is established technique for identifying and differentiating pharmaceutical polymorphs.
Importance of polymorphism in Pharmaceuticals
* Polymorphism has been recognized as an important element of drug development
* Polymorphic forms of a drug substance can have different chemical and physical properties, including melting point, chemical reactivity, apparent solubility, apparent solubility, dissolution rate, optical, electrical and mechanical properties, vapor pressure, stability, and density.
* These properties can have a direct effect the ability to process and/or manufacture the drug substance and the drug product, as well as on drug product stability, dissolution, and bioavailability. Polymorphism is very common among pharmaceutical substance and thermodynamic stability of a polymorph can impact pharmaceutical properties such as bioavailability, process ability and manufacturability.
* Polymorphic forms possess higher potential energy with respect to the thermodynamically stable or lowest entry forms.
* Different polymorphic phase’s exhibit unique physicochemical properties include solubility, dissolution rates...