Physicochemical Characterization, Compatibility and Stability Assessment of Lenvatinib Mesylate Using Thermal and Liquid Chromatography–Mass Spectrometry Techniques

This study was designed to quantitatively characterize lenvatinib mesylate and assess its compatibility with different excipients used in the preparation of solid, liquid, and advanced drug delivery dosage forms. The excipients evaluated were magnesium stearate, sodium starch glycolate, croscarmellose sodium, pregelatinized starch, microcrystalline cellulose, pluronic acid, stearic acid, and sodium taurocholate. To investigate drug–excipient compatibility, accelerated stability testing, isothermal stress testing, thermogravimetric analysis, differential scanning calorimetry, high-performance liquid chromatography, powder X-ray diffraction, and Fourier-transform infrared spectroscopy were employed. Differential scanning calorimetry indicated potential interactions between the drug and magnesium stearate, sodium starch glycolate, pregelatinized starch, pluronic acid, stearic acid, and sodium taurocholate. Isothermal stress-testing studies indicated that the lenvatinib content decreased by no more than 10% in the binary mixtures with magnesium stearate, sodium starch glycolate, croscarmellose sodium, pregelatinized starch, and microcrystalline cellulose after storage at 50 °C. In contrast, the pluronic acid, stearic acid, and sodium taurocholate mixtures showed substantial decreases in drug content, with values of 82.38 ± 0.191%, 83.17 ± 0.108%, and 79.84 ± 0.250%, respectively, indicating potential drug–excipient incompatibility under the investigated conditions. An ion observed at m/z 465.0616 under isothermal stress-testing conditions was assigned as a potassium adduct of the drug ([Lenvatinib + K]+) rather than a separate degradation impurity. These findings provide useful preformulation information for excipient selection in solid, liquid, and advanced drug delivery formulations and support further stability evaluation, degradation product characterization, impurity monitoring, and drug product development.