Wednesday, June 07, 2023

Chemistry of Polymorphism

Chemistry of Polymorphism

Polymorphism, a term derived from the Greek words for “much/many” and “form” (morphe), is used in disciplines as diverse as linguistics, computer science, biology, genetics and crystallography. In the life sciences industry, two completely different types of polymorphism play a major role: polymorphisms in DNA sequence and polymorphs of crystalline substances. In the former, great strides are being made using polymorphisms in their DNA sequence to predict an individual’s susceptibility to disease and response to drugs, making it possible to design and select appropriate drugs.

In the latter, the polymorphic form of a drug substance or excipient can profoundly impact a spectrum of aspects, such as biological action, production, formulation and intellectual property protection. Increasing recognition of the importance of polymorphism to the life sciences industry has generated a great deal of interest, and the field has been evolving rapidly. Given the pace of recent developments, an update is useful and timely.

Types of Polymorphism

Polymorphism occurs frequently because molecules frequently rearrange themselves into various shapes. We may divide polymorphism into two main types in chemistry based on how stable solid crystals are under various pressure and temperature conditions.

Mono-tropic Polymorphism: One polymorph is stable at all permissible temperatures in the mono-tropic system of polymorphism. This kind of polymorphism is present in the chemical metolazone.

Enantiotropic Polymorphism: There are various polymorphs in the enantiotropic system of polymorphism, and each polymorph is stable within a particular temperature range. As a result, one polymorph may be stable at low temperatures, another at high temperatures, and so on. This kind of polymorphism is present in the drugs carbamazepine and acetazolamide.

For the manufacture of medicine, polymorphism is very helpful in the pharmaceutical industry. The efficiency of the medicine and any potential adverse effects on the body are dependent on the solid crystal’s structure. One polymorph may be more therapeutically effective than another of the same substance and usage because polymorphs vary in their solubility.

Although the solutions and vapours of the many polymorphs of a substance appear the same, they each have unique physical and chemical characteristics. Physical characteristics like melting point, colour, hardness, density, electrical conductivity, hygroscopicity, latent heat of fusion, solubility and dissolution rate, as well as variations in chemical reactivity, can fluctuate significantly between different polymorphs of a substance.

Factors Affecting Polymorphism

The composition or mixing of various lipid components and polymorphism, which depends on variations in fatty acid moieties, are the most significant internal factors. Thermal treatment, additives, shear application, sonication and pressure are significant external factors.

Different polymorphs have varying stabilities. Some convert quickly, whether it’s warm or cold. The lattice energy of the majority of polymorphs of organic molecules barely varies by a few kJ/mol. Stability differences of more than 10 kJ/mol are uncommon, with most known polymorph pairings differing by less than 2 kJ/mol in 50% of cases.

The polymorph’s nature is influenced by the solvent in every way. In nature, concentration is present. Additional solvent constituents, such as species, encourage or hinder specific development patterns. The temperature of the solvent used to carry out crystallisation is frequently a significant influence.

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