Forced Degradation Study and Challenges in Analytical Method Development and Validation | Part I

Photolytic Degradation

Photolytic degradation is a type of forced degradation that occurs when a drug molecule is exposed to light.

 

The photolytic degradation process typically involves three steps:

1. Light Absorption: The first step in photolytic degradation is the absorption of light by the target molecule. Different molecules have varying abilities to absorb light of different wavelengths, depending on their electronic structure. When a molecule absorbs light energy, it undergoes an electronic transition from its ground state to an excited state.

 

2. Photochemical Reaction: In the excited state, the molecule becomes highly reactive and undergoes a photochemical reaction.

 

3. Decomposition or Modification: The final step involves the decomposition or modification of the molecule, resulting in the formation of different chemical species.

 

The light energy causes the drug molecule to break apart into smaller pieces. This can happen if the drug molecule contains bonds that are weak enough to be broken by light energy.

 

For example, the drug molecule carbamazepine contains a nitro group, which is a weak bond. When carbamazepine is exposed to light, the nitro group can break apart, forming two smaller molecules.

 

The rate of photolytic degradation can be affected by a number of factors, including the wavelength of light, the intensity of light, and the length of exposure. In general, shorter wavelengths of light, such as ultraviolet (UV) light, have more energy than longer wavelengths of light, such as visible light.

 

This means that UV light is more likely to cause photolytic degradation than visible light. The intensity of light also affects the rate of photolytic degradation. The higher the intensity of light, the faster the rate of degradation.

 

Photo-stability: Photostability, on the other hand, refers to the ability of a substance to resist degradation or undergo minimal chemical changes when exposed to light. It indicates the capacity of a compound to maintain its identity, potency, and quality during exposure to light.

 

Assessing the photostability of pharmaceuticals is essential for ensuring product integrity and longevity. Photostability testing helps in determining appropriate packaging materials, storage conditions, and expiration dates for pharmaceutical products.

 

By conducting photolytic degradation studies, the pharmaceutical industry can gain insights into the drug’s stability, identify degradation pathways, develop stability indicating method and implement appropriate measures to ensure product quality, efficacy, and safety. These studies contribute to the development of effective formulations, packaging materials, and storage conditions for pharmaceutical products.

 

Heat Degradation

Heat degradation is a common type of forced degradation used to assess the stability and potential degradation pathways of pharmaceutical drugs.

 

• Elevated temperatures can accelerate chemical reactions, leading to the breakdown of active pharmaceutical ingredients (APIs) and the formation of degradation products.
• The extent and specific degradation products may vary depending on the drug formulation, storage conditions, drug-specific characteristics, and duration of exposure to elevated temperatures.
• Proper storage and handling of pharmaceuticals are crucial to ensure their stability and efficacy.

 

Temperature: Samples are often heated to temperatures of 60-80°C for at least 1-7 days (not limited to, it depends on drug-specific characteristics).

 

This type of degradation can be caused by a number of factors:

• The breakdown of chemical bonds in the drug molecule
• The formation of new chemical bonds
• The loss of water molecules
• The oxidation of the drug molecule

 

Example

Cefazolin: Heat degradation of cefazolin can result in the formation of degradation product and leads to loss of potency.

 

Heat degradation of pharmaceutical drugs is the process by which the active ingredients in a drug break down when exposed to heat. This can happen during the manufacturing process, transportation, or storage of the drug. Heat degradation can lead to,

• The drug may change colour, texture, or solubility, making it difficult to administer.
• Heat degradation can lead to the loss of efficacy of the drug, which means that it will not be able to treat the condition for which it was prescribed.
• Heat degradation can also produce toxic byproducts, which can be harmful if ingested.

 

For these reasons, it is important to take steps to prevent heat degradation of pharmaceutical drugs. This includes storing drugs in a cool, dry place and avoiding exposure to direct sunlight. It is also important to follow the manufacturer’s instructions for storage and handling.

 

Read also:

• Forced Degradation Study and Challenges in Analytical Method Development and Validation | Part II
• Forced Degradation Study and Challenges in Analytical Method Development and Validation | Part III

 

Resource Person: Vadivelan Elangovan