Chemistry of Drug/degradants and control of drug degradation (Part-I)

Drugs are organic/inorganic/biological molecular entities. Control or minimization of drug degradation requires a clear understanding of the underlying organic chemistry of drug degradation, which is not only critically important for developing a Scientist but also for maintaining the quality, safety, and efficacy of an approved drug product over its product life cycle. Specifically, the knowledge of drug degradation is not only vital for developing adequate dosage forms that display favorable stability behavior over the registered product shelf life, but also critical in assessing which impurities would be most likely to be significant or meaningful degradants so that they should be properly controlled and monitored.

Degradation pathways with an emphasis on the underlying mechanisms of the degradation that tends to occur under the real-life scenarios, that is, the long-term storage conditions as represented by the stability conditions recommended by the ICH & WHO of Technical Requirements for approval of Pharmaceuticals for Human Use. The utility and limitation of stress studies or forced degradation in ‘‘predicting’’ real life drug degradation chemistry is cleared. optimization and avoiding degradation routes that could result in potentially harmful degradants should be made easier with a solid understanding of drug degradation chemistry.

Inadvertently contact to catalyst, Drug Substance, or drug product during transfer/ scale up or transfer of product to CMO’s. Evaluation and assessment of process/facility, process characterization is ineffective leads DS/DP degradation, correction to equipment/facilities.

There is most common pathway for drug degradation:

·???????? Hydrolytic degradations

·???????? Oxidative degradations

·???????? Unpredicted reaction like Autoxidative photochemical chemical degradation of drugs/biological drugs.

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These pathways of degradation are well known and can evaluate during DS & DP development.

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