Appropriateness of Dissolution Methods on Evaluation of Digoxin Product Quality

The objectives of the present work were to simultaneously quantify digoxin (DGX) and its impurities by a common analytical method, compare dissolution data of a FDA approved commercial products by DGX tablets USP monograph, and apply the developed method to assess quality of the product. A UPLC method was developed and validated as per ICH guideline. An FDA approved formulation of DGX tablets was evaluated for quality (assay and dissolution), and stability by storing it at 30 °C/75% RH and 40 °C/75% RH conditions. Dissolution testing was performed in water and 0.1 N HCl as per the USP monograph. The UPLC method was specific, and linear over 100-2000 ng/ml with good accuracy > 98.6% and precision < 3.3% for all the analytes (DGX, digoxigenin, digoxigenin monodigitoxoside and digoxigenin bisdigitoxoside). The tablets met USP specification of assay > 98% and dissolution of > 85% in 20 min in water medium. However, the drug degrades into impurities in the acidic medium and fluorospectrometric method was non-specific in quantifying drug and impurities as per the USP monograph. Dissolution decreased by almost 30% on exposure to stability conditions and did not meet the specification due to an increase in the drug crystallinity as supported by the X-ray powder diffraction data. In summary, the developed UPLC method can be applied to assess the quality of DGX tablets, and dissolution testing in the acidic medium and fluorospectrometric method was non-discriminatory and non-specific for routine quality control test.