Drug Degradation Prediction, In Silico Toxicity Assessment and Development of Stability-Indicating, Quality by Design Enabled UFLC Method for Sacubitril-Valsartan.

Stability and impurity profiling of drugs is crucial in fixed-dose drug combinations as safety, efficacy, and purity depend on an individual drug's stability behaviour. The formation of drug degradants is lean-on various factors and the probabilities of drug degradation may increase in fixed-dose drug combination formulations. Additionally, drug impurity profiling can be studied with the aid of degradation prediction. In this context, a preliminary attempt was made to use Zeneth software to anticipate the degradation of combination medications. Due to the presence of mutagenic/carcinogenic impurities i.e. NDMA/NDEA in various batches of Valsartan, FDA announces a recall in the last few years. Therefore, Zeneth predictions were performed to explore the effect of the presence of mutagenic impurity (NDMA/NDEA) on the stability of drug. The toxicity of each predicted degradant was evaluated with the help of TEST, ProTox II and Lazar toxicity prediction tools. In the present work, the stability behavior of combination drugs was evaluated with the newly developed QbD enabled UFLC method. Sacubitril and Valsartan were subjected to various stress degradation conditions like acid, base, oxidative, thermal, and photo stress environment alone and in fixed-dose combinations to assess the stability. [ABSTRACT FROM AUTHOR]