Forced degradation studies stability-indicating method

Zhang et al. [43] developed and validated a stability indicating HPLC method for the determination of lornoxicam in pharmaceutical formulation. The isocratic procedure was performed in Shimadzu ODS (4.6 mm x 15 cm, 5 pm) column maintained at 25 °C. The mobile phase was degassed mixture of sodium acetate (0.05 mol/L, pH 5.8) and methanol (55 45). The flow rate was 1 ml/min and detection at 290 nm. Selectivity, specificity, linearity, precision, accuracy, and robustness were evaluated to validate the analytical method. Forced degradation studies were performed to provide an indication of the stability-indicating capacity. The stability indicating method for lornoxicam in the injectable dosage was developed and validated. The method can be considered for routine analysis and quality control of lornoxicam in injectable formulation. 

Ruan, J., Tattersall, P, Lozano, R., and Shah, P. (2006). The role of forced degradation studies in stability indicating HPLC method developmerWm. Pharm. Rev., 9, 463. 

Chapter 7 focuses on how to develop stability indicating methods for API as well as drug products. It also discusses forced degradation studies that challenge the stability indicating power of analytical methods. 

Forced degradation samples are used in the process of developing stability-indicating methods early in development prior to initiating formal stability studies. The samples are analyzed for API peak purity (coeluting impurities), specificity, and mass balance. Efforts are also focused on determination degradation pathways/mechanisms for API and DP. 

Many potential degradation products are not observed in protein pharmaceuticals, primarily because much care is taken in the choice of formulations, lyophilization, and storage conditions in order to maintain protein stability. Thus, degradation is minimized and usable shelf lives are on the order of years. In order to study the degradation pathways of a biopharmaceutical protein, and to evaluate the stability-indicating ability of the analytical methods, it is sometimes necessary to perform forced degradation studies, where the biopharmaceutical protein is subjected to a variety of stress conditions, such as varying pH, elevated temperature, or the addition of oxidants. 

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