Stability of Drug Substances

The most easily understood and most studied form of drug instability is the loss of drag through a chemical reaction resulting in a reduction of potency. Loss of potency is a well-recognized cause of poor product quality. 

---

QID, Bracketing and matrixing designs for stability of drug substances and drug products, ICH, Brussels. 

Tingstad J, Dudzinski J. Preformulations studies II stability of drug substances in solid pharmaceutical systems. J Pharm Sci 1973 62(11) 1856—1860. 

In a recent review, Shan and Zaworotko have discussed cocrystals having pharmaceutical interest, and presented several case studies that they used to demonstrate how one could enhance the solubility, bioavailability, and/or stability of drug substances [23]. The systems considered were the cocrystals of fluoxetine hydrochloride with carboxylic acids, itraconazole with dicarboxylic acids, sidenafil with acetylsalicylic acid, and melamine with cyanuric acid. One main conclusion advanced by the authors was that the use of cocrystal systems in pharmaceutical dosage forms was inevitable, and that the main questions were who would benefit and how drastic the influence on development would ultimately turn out to be. 

The specifications for drug substance, drug product, packaging components, excipients, and so on will be established based on sound technical justification, using a continuously expanding experience base that includes information on process, product, analytical methods, stability of drug substance and produces), packaging components, and so on. 

Stability of Drug Substance During Manufacturing Process and Product Shelf-Life... 

To avoid or limit problems in this area after submission of the NDA, the validation of analytical methods and the conduct of stability studies should be planned from the initial phases of clinical research. This will provide the type of data approvable by FDA. The reader is directed to the Guideline for Stability Studies for Human Drugs and Biologies and the final ICH Guideline for the Stability of Drug Substance and Drug Product for assistance in fulfilling this essential requirement. 

Other examples where buffers were successfully used to study the pH stability of drug substances (and where... 

Berglund, M., Bystroem, K., and Persson, B. Screening chemical and physical stability of drug substances./. Pharm. Biomed. Anal. 8 639-643, 1990. 

Photochemical reactivity of drug formulations is an important aspect to consider during development, production, storage, and use of pharmaceutical preparations. However, photochemical stability of drug substances is rarely as well documented as thermal stability of the compounds. For instance, in order to obtain a high sterility assurance level of the product, a parenteral preparation is sterilized in its final container if possible. Steam sterilization at minimum temperature of 121°C for... 

---