2. Definition:
• Derived from Greek word
Poly means many & morph means shapes
• When a substance exist in more than one crystalline form, the
different forms are designated as polymorphs and the
phenomenon is known as Polymorphisms.
• due to different arrangements or conformations of the
molecules in the crystal lattice.
• More than 50% of active pharmaceutical ingredients (APIs)
are estimated to have more than one polymorphic form
3. Examples:
•
yellow laminar crystals. On cooling, the yellow form reverts to
red form.
•Paracetamol exist in two polymorphic forms. One is monoclinic
Form-I, which is marketed whereas Form-II is orthorhombic.
•Piroxicam, a nonsteroidal, anti-inflammatory drug widely
prescribed all over the world exists in three forms I, II and III.
5. Physical Properties Differ Among Various
Polymorphs
Difference in crystalline structure will leads to difference in
various physical properties
•packing properties
•thermodynamic properties such as free energy, solubility,
melting point, etc
•kinetic properties such as rate of dissolution, stability
•mechanical properties such as compatibility, hardness,
tensile strength, flow of material etc.
6. Stablity characterstics:
• Depending on their relative stability, one of the several
polymorphic form is more stable.
Stable polymorphisms
Metastable form
• Metastable to Stable due to their higher energy state.
7. Types of Polymorphisms
Polymorphism can be classified in to two types according to their
stability with respect to the different range of temperature and
pressure.
•Enantiotropic polymorph
If one form is stable over certain pressure and temp range,
while the form is stable over different pressure and temp range
e.g : sulfur
one polymorphs can change reversibly into another at
definite transition temp below the melting point
8. Types of Polymorphisms
• Monotropic polymorph
Only one polymorph is stable at all temperature below melting
point, with all other polymorph being unstable
e.g: chloramphenicol palmitate
No reversible transition is possible
11. Applications
• influence variety of API properties including flowability,
tableting, dissolution rate, solubility, stability and even
biological performance including efficacy and toxicity.
eg: six polymorphs of cocoa butter and all the polymorphs
have significantly different melting points
• enhance the shelf-life of the product & will help to
maintain the potency, as planned/desired
• Metastable form shows better bioavailability and therefore
preferred in formulations. Only 10% are in metastable
form
12. • The effect of polymorphisms on bioavailability, if bioavailability
is mediated by dissolution
e.g: chloramphenicol palmitate, aspirin, novobiocin etc
• polymorphisms of excipients in bioavailability
13. References:
1 Raza K, Kumar P, Ratan S, Malik R, Arora S (2014)
Polymorphism: The Phenomenon Affecting the
Performance of Drugs. SOJ Pharm Pharm Sci, 1(2), 10.
•Grant DJW. [Chapter 1]. Theory and origin of
polymorphism. Polymorphism in pharmaceutical solids. In:
Brittain Harry G, editor. Marcel Dekker, Inc; 1999.
•www.wikkipedia.com
