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The current study aimed to investigate drug carrier miscibility in pharmaceutical solid dispersions (SD) and include the effervescent system, i.e. Effervescence-induced amorphous solid dispersions (ESD), to enhance the solubility of a poorly water-soluble Glibenclamide (GLB). Kollidon VA 64, PEG-3350, and Gelucire-50/13 were selected as the water-soluble carriers. The miscibility of the drug-carrier was predicted by molecular dynamics simulation, Hansen solubility parameters, Flory-Huggins theory, and Gibb’s free energy. Solid dispersions were prepared by microwave, solvent evaporation, lyophilization, and Hot Melt Extrusion (HME) methods. The prepared solid dispersions were subjected to solubility,  in-vitro  dissolution, and other characterization studies. The  in-silico  and theoretical approach suggested that the selected polymers exhibited better miscibility with GLB. Solid-state characterizations like FTIR and  1 H NMR proved the formation of intermolecular hydrogen bonding between the drug and carriers, which was comparatively higher in ESDs than SDs. DSC, PXRD, and microscopic examination of GLB and SDs confirmed the amorphization of GLB, which was higher in ESDs than SDs. Gibb’s free energy concept suggested that the prepared solid dispersions will be stable at room temperature.  Ex-vivo  intestinal absorption study on optimized ESDs prepared with Kollidon VA64 using the HME technique exhibited a higher flux and permeability coefficient than the pure drug suggesting a better drug delivery. The drug-carrier miscibility was successfully studied in SDs of GLB. The addition of the effervescent agent further enhanced the solubility and dissolution of GLB. Additionally, this might exhibit a better bioavailability, confirmed by  ex-vivo  intestinal absorption study.

Effervescence-induced amorphous solid dispersions with improved drug solubility and dissolution