Effect of hydrophilic polymer on solubility and taste masking of linezolid in multi-component cyclodextrin inclusion complex: Physicochemical characterization and molecular docking

Abstract

The current work deals with the effect of hydrophilic polymer in a multi-component β-cyclodextrin (βCD) inclusion complex for enhancement of solubility and taste masking ability of linezolid (LZ). The phase solubility studies indicated the formation of 1:1 M stoichiometric ratio of LZ to βCD in all complexes in presence or absence of hydrophilic polymer (HPMC e5LV). The high stability constant (Ks; 1089 M−1, 1393 M−1), complexation efficiency (CE; 3.347, 3.761) and more negativity of Gibbs free energy (ΔG; −238.69, −1019.61) of ternary complexes in presence of 2.5% w/v and 5% w/v of HPMCe5LV was compared with binary system (Ks, 1024 M−1: CE, 2.571: ΔG, −59.91), which resulted in the improved complexation stability and solubilizing efficiencies. Solid inclusion complexes of LZ-βCD were prepared in 1:0.3 M ratio by kneading, co-evaporation, physical mixing and microwave irradiation methods with or without addition of HPMC e5LV. The drug content, solubility, dissolution and taste masking of LZ in ternary complexes were significantly higher (p < 0.05) than the binary complexes. The lowest MDT value (0.34 ± 0.007), highest value of DE (30mts) (28.9 ± 0.05) and R (15mts) (70.33 ± 0.57) were observed in case of solid inclusion complexes prepared by microwave irradiation method. The negative binding affinity found in molecular docking indicated the high stability of the ternary complex. No interaction was found in LZ, βCD and HPMC e5LV when analyzed by FTIR study. XRD and DSC results revealed that more amorphization of LZ in presence of βCD and HPMC e5LV. It infers that the multi-component system by microwave irradiation method can be a promising approach for increasing solubility with better palatability.