Background: Efavirenz is the most used medication in the treatment of Acquired Immunodeficiency Syndrome (AIDS). The limited number of pediatric antiretroviral formulations approved by regulatory agencies is the most significant obstacle to adequate and efficient pharmacotherapy for this group of patients. The efavirenz has excellent therapeutic potential, but has low aqueous solubility/bioavailability. Methods: To minimize these limitations, multicomponent systems with β-cyclodextrin and polyvinylpyrrolidone K-30 were obtained. Due to the limited number of pediatric antiretroviral formulations, the development of a pediatric orodispersible tablet is an alternative that is thought easy to administer, since it disintegrates rapidly in the oral cavity. The multicomponent systems were obtained by the method of kneading and characterized by solubility test, X-ray diffraction, differential scanning calorimetry and infrared absorption spectroscopy by Fourier transform. The orodispersible tablets were prepared by direct compression. The quality control of hardness, friability, disintegration, and dissolution was performed. The influence of the components of the formulation on the characteristics of the tablets was evaluated through a 22 factorial design added with three central points, to compare the effect of the dependent variables on the responses. Results: An increase in drug solubility was observed, with a decrease in crystallinity. Besides that, an excellent dissolution profile presented with more than 83% of the drug's content dissolved in less than 15 minutes. Satisfactory disintegration time and friability were observed. Conclusion: It was observed that reduced concentrations of mannitol decreased the hardness and disintegration time of the formulations. The orodispersible tablet composed of efavirenz: β- cyclodextrin: polyvinylpyrrolidone, favors greater absorption and bioavailability. It has several advantages for pediatric patients, as the dosage form disintegrates quickly in the mouth and does not require water for administration, thereby improving patient compliance with the treatment.