Analytical Method Development and Forced Degradation Studies on Proteasome Inhibitor: Bortezomib As A Part of Preformulation Study to Develop Stable Lyophilized Dosage Form

Forced degradation study is an important tool to identify the degradation of the drug substance1 when subjected to different stress conditions which is more useful than the accelerated stability testing during the formulation development. A simple and stability indicating HPLC method was developed for the characterization of assay and related substances of the drug substance. In the present investigation, bortezomib was subjected to different stress conditions like acid hydrolysis, base hydrolysis, oxidation, effect of heat and effect of light. Significant degradation was observed when Bortezomib sample solutions are exposed to acidic conditions and basic at room temperature. Drastic degradation was observed when bortezomib sample solutions are exposed to oxidation. Significant degradation was observed when bortezomib sample solution is exposed to heat at 60°C and exposed UV radiation. Solid state degradation data indicates that bortezomib has insignificant degradation upon exposure to UV light. The proposed analytical methods enable accurate, precise, and rapid analysis of Bortezomib. Stress study results helps in opting the solvents for the compounding process with respect to stability of the compound. Based on the stress study data, the product can be lyophilized in clear glass vial for the future prospective of novel lyophilized formulation.