Аннотация:Dexamethasone (DEX) is a corticosteroid drug used to treat arthritis, asthma, and considered as a promising drug for the treatment of Covid-19. The major drawback of DEX is its poor aqueous solubility (89 mg/mL). In order to enhance its solubility, polymorph and cocrystal screening were executed that resulted the crystallization of the metastable polymorph (commercial Form A) along with two novel cocrystals with catechol (CAT) and resorcinol (RES). These solid forms were characterized by powder-XRD, DSC, and single crystal XRD. The commercial Form A (P212121, Z'=1, new) and reported Form B (P212121, Z'=2) were harvested concomitantly during crystallization from CH3CN. While Form A constitutes trimer ring motif, Form B maintains dimer between two symmetry independent DEX molecules and they are designated as synthon as well as packing polymorphs. Presence of CAT/RES, breaks the dimer/trimer synthons in the cocrystal lattice of the drug molecule and forms a hydrogen bonded sandwich between two anti-parallel DEX chains. In addition, both DEX‒CAT and DEX‒RES are proved to be isostructural cocrystals based on their identical lattice parameters and molecular packing arrangement. Aqueous solubility (24h) experiments indicated that the commercial Form A was 1.5 fold more soluble than that of Form B and inversely correlated with their melting points. DEX‒CAT and DEX‒RES cocrystals improved aqueous solubility by 2-5 fold than the commercial Form A, although both the cocrystals transformed to the mixture of polymorphs during solubility experiments. Improved solubility of the DEX‒CAT cocrystal may offer more bioavailability of DEX.