Forced degradation studies development

Harmon PA. Development of a peroxy radical mediated oxidative stressing system for predicting general oxidative sensitivity in solid dosage forms. Forced Degradation Studies Best Practices for the Pharmaceutical Industry. Institute for International Research, Princeton, NJ, Feb 24-25, 2004. 

Forced degradation/stress studies elucidate the inherent stability characteristics of the molecule under study and determine its degradative pathways. Forced degradation studies are needed to support method validation, determine product protection requirements, and guide formulation development. 

To support method validation. Forced degradation studies provide the degradation products that are the basis for the development and... 

Forced degradation studies on the API are generally done early in the development program on a single batch. The FDA IND Phase 2/3 Guidance recommends that these studies be carried out in phase 2. 

Failure to carry out appropriate forced degradation studies can result in compliance issues. If forced degradation products are not generated and included in method validation studies, those methods maybe deemed unvalidated and all results generated using those methods could be questioned. If an unknown peak is observed later in the development program as the result... 

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. 

The guideline calls for "forced degradation" studies and a "confirmatory" study. Forced degradation studies should be carried out early in the formulation development process to evaluate overall photosensitivity. 

The number of experiments and the experimental design of photostability studies conducted under the "forced degradation studies" are left completely to the judgment of the applicant. Careful studies designed to discover photostability problems early in development could provide significant savings by avoiding costly surprises later on. 

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