A Converged Pharmaceutical Analysis Supported with Hydrotropy & DoE with dual HPTLC and Stress Studies for Estimation of Tolvaptan

Abstract The article introduces an inventive, eco-friendly, simple, consistent and coalescing TLC-Densitometry approach to a pharmaceutical estimation of Tolvaptan in the bulk and tablet matrix. For successful sample preparation and further analysis in both normal and reverse- phases, hydrotropic solubilization was chosen. The determination was performed employing densitometric estimation using ultraviolet exposure at 271 nm. The separation was achieved on (10 × 10 cm) aluminum backed silica gel 60-F254 and RP-18 F254S as stationary phases separately. Optimized mobile phases were carbon tetrachloride: methanol (3.5: 1.5 v / v); acetonitrile: water (3: 2 v / v) for normal and reverse phase modes respectively. Dual quantitation was conducted over a concentration range of 300-1800 ng/band. The compact and well-resolved bands for the Tolvaptan standard and samples were obtained in both methods at a retention factor (Rf) value of 0.39 ± 0.2 and 0.42 ± 0.2 respectively. In order to examine the stability-indicating characteristics of the process, the compound was subjected to acidic and alkaline, oxidative, film, thermal (dry heat) and neutral stress conditions. Extensive loss has been observed in conditions with acidic, alkaline and oxidative stress. Box-Behnken design was applied as a DoE approach to evaluate method robustness and to ensure system efficiency. The methods developed were validated according to the International Conference on Harmonization (ICH) for accuracy, robustness and ruggedness.