Objective: The objective of the research was the preparation and evaluation of methotrexate nanoemulsion to improve its solubility, permeability, and bioavailability. Methods: The formulation components were selected based on the solubility study, and the pseudo-ternary phase diagrams were constructed by the aqueous phase titration method. Result and discussion: The prepared nanoemulsions were exposed to several thermodynamic stability studies and then to many characterizations tests for the selection of the best formulation. F 11 is the best formula since it has a 57 nm globule size, 0.21 polydispersity index, +23.67 zeta potential, and 99.57% light transmittance. FTIR study confirmed no incompatibility between drug and excipients. Conclusion: F 11 was a promising nanoemulsion formula that improved methotrexate permeability and bioavailability.
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