Breast cancer treatment is a global health challenge using conventional toxic chemotherapeutic agents. A novel isatin could be a promising alternative. An isatin derivative (TM-19) was synthesized and characterized using NMR (nuclear magnetic resonance), mass spectrometry, Fourier transform infrared (FTIR), and differential scanning calorimetry (DSC). HSPiP and GastroPlus predictive software were used to predict suitable solvents for solubility and in vivo oral pharmacokinetics in humans (fasted condition), respectively. Based on predictive findings, topical elastic liposomes (phosphatidylcholine as PC and span 80 by film hydration method) was prepared, characterized, and optimized using QbD (quality by design). QbD identified the impact of composition on response variables (Y₁ for size, Y₂ for polydispersity index, Y₃ for zeta potential, and Y₄ for %EE). In vitro cytotoxicity study was carried out against MCF-7 cell lines. Low molecular weight and lipophilic TM-19 was crystalline in nature (255 g/mol). GastroPlus program predicted limited in vivo dissolution and poor oral absorption (10.4 %). Results confirmed the highest TM-19 solubility in DMSO (dimethyl sulfoxide) ˃ chloroform ˃ PEG 400 (polyethylene glycol 400). Considering experimental and predicted data, topical delivery of TM-19 using optimized (desirability parameter value = 0.97) elastic liposomes (TF1) was quite promising due to optimal size (344 nm), high %EE (61.7 %), low PDI (0.45), and optimal zeta potential (− 12.34 mV). TM-19 loaded TF1 elicited concentration dependent cytotoxic effect (˃ 90 % at 10 µM) against MCF-7 as compared to TM-19 suspension.