Desloratadine (DSL) is an anti-allergic agent but its efficacy is limited with its low dissolution rate and aqueous solubility results in restricted bioavailability. The current study examines the probability of using Kolliphor(R) 188 (K188) and Pluronic(R) F127 (P127) as solubility improving agents of DSL that can be used to formulate in situ gel systems intended for nasal application in order to extend the contact time with nasal cavity and thereby maintain uptake of the drug. Solid dispersions (SDs) having various mass ratios of polymers and DSL were formulated using solvent-lyophilization method. SDs were evaluated for morphology, crystallinity, thermal behavior, solubility and dissolution rate to assess the efficiency of the polymers as solubility modifiers. SDs prepared with K188 and P127 demonstrated soft and fluffy structure, smaller particle size and narrower size distribution. DSC, FT-IR, H-1-NMR spectra confirmed the constitution of SDs and supplied information about the state of DSL in polymeric network. As the solubility of DSL was determined as 0.106 +/- 0.009, all SDs prepared with K188 and P127 displayed enhanced solubility from 42- to 115-fold. Drug dissolution rate of DSL for all SDs was remarkably higher than of the pure DSL. K1 and P1 formulations were selected as optimum for designing nasal in situ gel systems. Gels designed by cold method were determined to show modified release fitted best to Peppas-Sahlin model. The transparent gels designed using sufficient quantities of polymers can be reducing the mucociliary clearance appear to be a feasible alternative to commercially available DSL tablets..