Forced Degradation

Forced degradation studies are applied to demonstrate the chemical behavior of the molecule which may occur to degrade a processed product. These studies are usually conducted before final formulation as they can rapidly screen material stability by external stresses. It should be kept in mind that in the forced degradation studies, the degradation products generated in the stressed samples are termed as "potential" degradation products that may or may not be formed under relevant storage conditions.

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There are four major forced degradation in forced degradation studies: hydrolytic degradation, oxidative degradation, photolytic degradation and thermolytic degradation.

Fig. 1 Conditions generally used for forced degradation studies. (Rawat, 2015)

• Hydrolytic Degradation Studies

The degradation which is due to hydrolysis is Hydrolytic degradation. Hydrolysis reactions are typically acid or base-catalyzed. Therefore, acidic and basic conditions should also be employed in order to induce potential hydrolytic reactions apart from water. The hydrolytic degradations are recommended to be performed at a temperature of about 70\degc with a reflux condenser installed to avoid the loss of evaporation and using few glass beads or porcelain pieces to avoid bumping, conducting the stress reflux always in the fume hood.

• Oxidative Degradation Studies

Oxidative degradation is one of the most common mechanisms of drug degradation. Oxidative degradation is typically performed at room temperature in dark. Higher temperature is not recommended since the reaction rate in solution may actually be reduced at higher temperature due to a decrease in oxygen content of the solvent. Typical stress conditions: stress with 3% hydrogen peroxide for 24 hours or until about 5% to 20% degradation is achieved or whichever is earlier.

• Photolytic Degradation Studies

Photolytic degradation is the degradation that results from exposure to UV or visible light. The typical exposure conditions for this forced degradation study are exposing the samples 3 times to 1.2 million lux-hr visible and 200w-hr/m² UV.

• Thermolytic Degradation Studies

The thermolytic degradation studies involve different reactions like pyrolysis, hydrolysis, decarboxylation, isomerization, rearrangement and polymerization. These determines the melting point of the analyte. The general procedures include stressing for a week and observing the sample, testing the sample in between and achieving a degradation between 5% to 20%, if no degradation is achieved even after harsher stress, justification can be provided that molecule is stable.

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References

• Rawat, Trivikram, et al. "Forced degradation studies for drug substances and drug products-scientific and regulatory considerations." Journal of pharmaceutical Sciences and research 7.5: 238 (2015).
• Iram, Farah, et al. "Forced degradation studies." J Anal Pharm Res 3.6: 00073 (2016).