Polymorphism: Phase Change in Pharmaceutical Compounds

Polymorphism: Phase Change in Pharmaceutical Compounds

By Ashokbhai Patel

The word polymorphism is derived from Greek words “poly” meaning many, and “morph” meaning shape. Joining both words together, in Greek, its meaning is a system with many different shapes. Hence, polymorphism is the ability of the chemical molecule to pack in more than one different crystalline lattice phase. Polymorphism has a number of applications in electronics, food, and pharmaceutics.

Why Polymorphism Occurs

The main cause behind the occurrence of polymorphism is the different interactions between molecules while they are packing in the form of crystals, which results in a change in the dimensions, shape, volume of unit cell, number of asymmetric and symmetric units, and type of symmetry involved. These changes in the crystal structure imparts the difference in the physicochemical properties of the polymorphs. A well-known scientist, W. C. McCrone suggested that the “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”.

How Polymorphism Has Affected the Pharmaceutical Industry

After the discovery of polymorphism, an increasing number of studies have indicated the polymorphic nature of some inorganic and organic materials. In the last few decades, as a new method developed for screening for polymorphs, the number of newly reported polymorphs increase exponentially.

Intellectual property (patent) rights must be considered. For example, if one should find a form which has higher bioavailability, it should not infringe existing patents. Sometimes it is in organizations profit to file the patent protection for all other solid forms. However, formation of undesirable polymorph can lead to many costly mistakes, especially for pharmaceutical industries. For example, Ritonavir, an anti-HIV drug was marketed as Norvir capsules. Because of very poor solubility of Ritonavir, it was formulated in the form of soft gelatin capsules containing ethanol/water as a co-solvent. During the development phase of Ritonavir, only one crystal form (Form I) was identified. However, in mid-1998, in many cases, the capsules suddenly failed to meet up the required dissolution limits. X-ray diffraction studies performed on the content of the capsules revealed a new unidentified form of Ritonavir (Form II). Form II of Ritonavir was found to be most stable and least soluble, resulting in failure of dissolution tests.

To sum it all up, polymorphism is just another example of how phase changing materials are shaping the pharmaceutical industry. Register for our free Phase Change Webinar and discover what other industries are being disrupted by phase change materials.

Image courtesy of pixabay.com

Learn more about PreScouter at www.prescouter.com.

Never miss an insight

Get insights delivered right to your inbox

More of Our Insights & Work

Never miss an insight

Get insights delivered right to your inbox

You have successfully subscribed to our newsletter.

Too many subscribe attempts for this email address.