Study of Degradation Behavior of Active Pharmaceutical Ingredients

Abstract

Stability testing of drugs is mandated by regulatory body as well as health agencies of various countries across the globe. Since it will ensure quality of drug product throughout its shelf life. Hence by considering influence of stability on quality of drug it was endeavored to study degradation behavior of selected drugs. A comprehensive study of the stress degradation behavior of atorvastatin (ATR) and aspirin (ASP) was carried out in accordance with ICH guidelines, alone as well as in combination of 1:1 and 1:7.5 ratios, respectively. The degradation products of ASP as well as atorvastatin were successfully separated by a developed simple, selective, and precise stability-indicating reversed-phase HPLC method. The extent of degradation was significantly influenced when both of the drugs were present in combination. In addition the combination ratio of aspirin and atorvastatin also influenced the percentage degradation of each other. All the results indicate chemical incompatibility of both aspirin and atorvastatin if present in combination. A novel, simple, isocratic as well as LC-MS compatible RP-HPLC stability indicating assay method for tapentadol hydrochloride (TAP) was developed and validated. Forced degradation of TAP was carried out in accordance with ICH guidelines. TAP found stable under all forced degradation conditions, except oxidative stress. TAP showed two major degradation products in oxidative stress condition. Furthermore both oxidative degradation products were characterized with the help of LC-MS/MS technique. Furthermore its fragmentation pathway and plausible mechanism for generation of degradation product was also proposed. No previous report was available in the literature regarding the characterization of degradation product of TAP. A new, simple, isocratic as well as LC-MS compatible RP-HPLC stability indicating assay method was developed and validated for febuxostat (FBX) in bulk as well as in its pharmaceutical dosage form. FBX was found unstable under alkaline hydrolytic conditions, in all other stress conditions it was found stable. Alkaline degradation product was characterized by LC-MS/MS analysis. Furthermore fragmentation pathway of alkaline degradation product was laid down. Subsequently, possible mechanism for formation of generation of degradation product was also postulated. Developed and validated methods as mentioned above can be successfully employed in the routine quality assessments of these drugs in bulk as well its pharmaceutical dosage form.