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Polymorphism in general means having many forms. The term is used in chemistry to describe the ability of a chemical compound to crystallize in multiple unit cell configurations. It is of practical relevance to pharmaceuticals, agrochemicals, pigments, dyestuffs, foods, and explosives. Many compounds display polymorphism. It can be said that "every compound has different polymorphic forms, and that, in general, the number of forms known for a given compound is proportional to the time and money spent in research on that compound."
What is Polymorphism?
The IUPAC (International Union of Pure and Applied Chemistry) defines polymorphic transition as "A reversible transition of a solid crystalline phase at a certain temperature and pressure (the inversion point) to another phase of the same chemical composition with a different crystal structure.” Eilhardt Mitscherlich, a German chemist, discovered the differences in the crystalline forms of many elements and compounds in the 1820s.
Polymorphism
Friedrich Wöhler and Justus von Liebig saw that needles of freshly crystalized benzamide slowly changed into rhombic crystals. As of the present day, three polymorphs of benzamide have been identified.
Another example of polymorphism is the pair of minerals calcite and aragonite. Both are polymorphs of calcium carbonate.
Polymorphs of Calcium Carbonate
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Types of Polymorphism
According to the stability of polymorphs with respect to different ranges of temperature and pressure, polymorphism can be classified into two:
Monotropic System
In a monotropic system, only one polymorph is stable at all temperature ranges. A very good example of a monotropic system is metolazone.
Types of Polymorphism
Enantiotropic System
In an enantiotropic system, different polymorphs are stable across different temperature ranges. Examples of an enantiotropic system include carbamazepine and acetazolamide.
Factors Affecting Polymorphism
- Ostwald’s rule states that the less stable polymorphs crystalize before the more stable ones.
- Polymorphs have disparate stabilities. Some change rapidly at room temperature or any temperature.
- Polymorphism affects the rate of crystallization. The properties of the solvent affect the nature of the polymorph. For example, the concentration of the solvent and temperature.
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Differing Properties
Polymorphs of a compound can display different physical and chemical properties though, generally, the solutions and vapours can be identical. There can be substantial differences in melting point, colour, hardness, density, electrical conductivity, hygroscopicity, latent heat of fusion, solubility, and dissolution rate, and variance in chemical properties.
Polymorphs exhibit different properties in solid-state
Polymorphism and Allotropy
While polymorphism is the ability of a solid material to exist in more than one crystal structure, allotropy is the ability of chemical elements to exist in two or more different forms in the same physical state.
Allotropes of Carbon
In the case of crystal solids, allotropy is a particular case of polymorphism.
Polymorphs and Solvates
A solvate can be defined as a combination of a solute ion or molecule and one or more solvent molecules. A particular solvate can have many polymorphs. In thermodynamics, when the most stable anhydrous (containing no water) polymorph stops being the most stable, it changes into a solvate in the presence of the right solvent. The most stable solvate need not be the lowest level of the solvate.
Polymorphs and Solvates
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Applications of Polymorphism
A major application of polymorphism is in the pharmaceutical field. A factor in determining the effectiveness of a drug on the human body is the structure of the crystal of the drug. Also, knowledge of chemical properties such as solubility and stability is essential during the initial stages of drug development. Since polymorphs can vary in their solubility, one polymorph of a drug can be more successful than the other. In general, approval is often only granted for one polymorph of a drug.
Polymorphism is used in the Medical field
Examples of polymorphism in drugs and pharmaceuticals are mentioned below.
- The poor compressibility of paracetamol powder made the manufacturing of tablets difficult. This led to the research and discovery of a new polymorph of paracetamol.
- There are five different polymorphs of cortisone acetate. Four of these are soluble in water and produce a stable shape.
Polymorphs of Ritonavir
Ritonavir is an antiviral drug – an HIV protease inhibitor used in combination with other antivirals in the treatment of HIV infection. It interferes with the reproductive cycle of HIV. It has two polymorphs. One of them is inactive when compared to the other. It was discovered that the active polymorph transformed into the inactive polymorph upon contact with the inactive polymorph.
Polymorphs of Ritonavir
The reason for this transformation was the high stability and lower energy of the inactive polymorph. This was a problem because the inactive polymorph was worthless as a drug and just a little of it was enough to change large quantities of the active polymorph into the inactive polymorph. The massive production problem was finally solved by administering the drug through tablets and gel caps instead of capsules.
Things to Remember
- Polymorphism describes the ability of a chemical compound to crystallize in multiple unit cell configurations.
- Polymorphs can be divided into Monotropic System and Enantiotropic System based on stability with respect to different temperatures.
- In a monotropic system, only one polymorph is stable at all temperature ranges. In an enantiotropic system, different polymorphs are stable across different temperature ranges.
- Polymorphs of a compound can display different physical and chemical properties though, generally, the solutions and vapors can be identical.
- Allotropy is the ability of chemical elements to exist in two or more different forms in the same physical state. In the case of crystal solids, allotropy is a particular case of polymorphism.
- A solvate can be defined as a combination of a solute ion or molecule and one or more solvent molecules. A particular solvate can have many polymorphs.
- A major application of polymorphism is in the pharmaceutical field. A factor in determining the effectiveness of a drug on the human body is the structure of the crystal of the drug.
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Sample Questions
Ques. Explain the term Polymorphism. In chemistry, what is meant by the term? (2 marks)
Ans. The word polymorphism means having many forms. The term is used in chemistry to describe the ability of a chemical compound to crystallize in multiple unit cell configurations.
IUPAC (International Union of Pure and Applied Chemistry) defines polymorphic transition as "A reversible transition of a solid crystalline phase at a certain temperature and pressure (the inversion point) to another phase of the same chemical composition with a different crystal structure.”
Ques. Explain the two types of Polymorphism with examples. (3 marks)
Ans. According to the stability of polymorphs with respect to different ranges of temperature and pressure, polymorphism can be classified into two:
- Monotropic System
In a monotropic system, only one polymorph is stable at all temperature ranges. A very good example of a monotropic system is metolazone.
- Enantiotropic System
In an enantiotropic system, different polymorphs are stable across different temperature ranges. Examples of an enantiotropic system include carbamazepine and acetazolamide.
Ques. What is the difference between polymorphism and allotropy? (2 marks)
Ans. Polymorphism is the ability of a solid material to exist in more than one crystal structure. Allotropy is the ability of chemical elements to exist in two or more different forms in the same physical state.
In the case of crystal solids, allotropy is a particular case of polymorphism.
Ques. An important application of polymorphism is in the pharmaceutical field. True/False. Explain. (2 marks)
Ans. True. A major application of polymorphism is in the pharmaceutical field. A factor in determining the effectiveness of a drug on the human body is the structure of the crystal of the drug. Also, knowledge of chemical properties such as solubility and stability is essential during the initial stages of drug development. Since polymorphs can vary in their solubility, one polymorph of a drug can be more successful than the other.
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Ques. Give examples of instances of the use of polymorphisms in the field of pharmaceuticals. (2 marks)
Ans. • The poor compressibility of paracetamol powder made the manufacturing of tablets difficult. This led to the research and discovery of a new polymorph of paracetamol.
- There are five different polymorphs of cortisone acetate. Four of these are soluble in water and produce a stable shape.
Ques. When was the phenomenon of Polymorphism first discovered? (2 marks)
Ans. Eilhardt Mitscherlich, a German chemist, discovered the differences in the crystalline forms of many elements and compounds in the 1820s.
Ques. Explain the peculiar problem that occurred during the production of Ritonavir. How was it solved? (3 marks)
Ans. Ritonavir is an antiviral drug – an HIV protease inhibitor used in combination with other antivirals in the treatment of HIV infection. It interferes with the reproductive cycle of HIV. It has two polymorphs – one of them inactive when compared to the other. It was discovered that the active polymorph transformed into the inactive polymorph upon contact with the inactive polymorph. This was a problem because the inactive polymorph was worthless as a drug and just a little of it was enough to change large quantities of the active polymorph into the inactive polymorph. The massive production problem was finally solved by administering the drug through tablets and gel caps instead of capsules.
Read More: Atomic Mass of Elements
Ques. What is the relationship between solvates and polymorphs in thermodynamics? (2 marks)
Ans. In thermodynamics, when the most stable anhydrous(containing no water) polymorph stops being the most stable, it changes into a solvate in the presence of the right solvent. The most stable solvate need not be the lowest level of the solvate. A particular solvate can have many polymorphs.
Ques. What are the factors that affect polymorphism? (2 marks)
Ans.
- Ostwald’s rule states that the less stable polymorphs crystalize before the more stable ones.
- Polymorphs have disparate stabilities. Some change rapidly at room temperature or any temperature.
- Polymorphism affects the rate of crystallization. The properties of the solvent affect the nature of the polymorph. For example, the concentration of the solvent and temperature.
Ques. Do different polymorphs exhibit different properties? (2 marks)
Ans. Polymorphs of a compound can display different physical and chemical properties though, generally, the solutions and vapours can be identical. There can be substantial differences in melting point, colour, hardness, density, electrical conductivity, hygroscopicity, latent heat of fusion, solubility, and dissolution rate, and variance in chemical properties.
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