Nanoparticle engineering is a well-defined technique employed as a novel and effective method in drug design and delivery. It is widely used to control particle size, as well as the morphological and physicochemical properties of active pharmaceutical ingredients. Furthermore, it serves as a method of pre-dispersion preparation for various dosage form developments. Nanotechnology produces nanomaterials with enhanced properties in terms of solubility, dissolution and permeability. In this work, ultrasonic-assisted precipitation was employed to produce nanosuspensions of poorly water-soluble loratadine, using different stabilizers. The objective of our study was attempting to prepare solid nanoparticles of loratadine to be used as a possible intermediate for designing various dosage forms. The effects of the type(s) and concentration(s) of stabilizer(s) on mean particle size were assessed. Optimal process parameters required to produce homogeneous nanoparticles with particle size below 500 nm and polydispersity less than 0.3 were determined both for precipitation and ultrasonication. Pre-dispersions were evaluated for their particle size, polydispersity index and zeta potential. Freeze-drying was employed to produce dry nanoparticles. Particle size, particle size distribution and zeta potential of the dried nanoparticles were measured after reconstitution in water. Besides thermal analysis using DSC and structural analyses (XRPD and FT-IR), the morphological characteristics and dissolution behaviors were also investigated. The selected freeze-dried nanoparticles had a mean particle size range of 353–441 nm, a polydispersity index ranging between 0.167 and 0.229 and a zeta potential between −25.7 and −20.7 mV. These results suggest that material and process parameters were successfully optimized. DSC and XRPD spectra confirmed interactions between the formulation's components during freeze-drying. The solid nanoparticles showed 30–42% of cumulative release after 10 min compared to less than 1% of dissolution characterizing loratadine without pre-processing. This study demonstrates that preparing dried loratadine nanoparticles suitable for designing effective drug preparations is a feasible approach.