Purpose <p>Dapsone (DAP) is a bacteriostatic antibiotic classically used in the therapeutic regimen for leprosy (HANS). Its low solubility reduces the absorption rate, directly affecting bioavailability, requiring its association with matrices, such as layered double hydroxides (LDH).</p> Methods <p>The synthesis of LDH, molar ratio of 2:1 (M²⁺/M³⁺), was carried out associated with DAP by the one-pot coprecipitation method. The characterizations and performance were evaluated by XRD, FTIR, zeta potential, thermogravimetry, SEM, dissolution and MTT assay.</p> Results <p>XRD showed DAP adsorbed on the lamellae, with a reduction in the intensity of the crystallographic plane (003) and the Bragg and Scherrer equations were used to determine the crystallographic parameters d, t and c. In addition, cif files were indexed to the experimental data to evaluate the relationship between theoretical and experimental data. Scanning Electron Microscopy showed a less defined shape for LDH-DAP. Furthermore, FT-IR spectra suggested electrostatic interactions between the sulfonyl groups of DAP and the lamellae of LDH, confirmed by the change in zeta potential, drug loading (29.2%) and thermogravimetry (TGA-DTA). In simulated intestinal medium, a change in the DAP dissolution profile was observed, with the Baskar model being the most adjusted to explain the release of LDH-DAP over 8&#xa0;h of experiments. Furthermore, biocompatibility was proven in the MTT assay in epithelial macrophages, making them therapeutically promising.</p> Conclusion <p>Thus, LDH-DAP was able to modify the crystal structure and dissolution rate of DAP and can be considered a promising hybrid system for future applications in the pharmaceutical field.</p> Graphical Abstract <p></p>