Development and evaluation of lafutidine solid dispersion via hot melt extrusion: Investigating drug-polymer miscibility with advanced characterisation

摘要

Abstract In current study, immediate release solid dispersion (SD) formulation of antiulcer drug lafutidine (LAFT) was developed using hot melt extrusion (HME) technique. Amphiphilic Soluplus? used as a primary solubilizing agent, with different concentrations of selected surfactants like {PEG} 400, Lutrol {F127} (LF127), Lutrol {F68} (LF68) were used to investigate their influence on formulations processing via HME. Prepared amorphous glassy solid dispersion was found to be thermodynamically and physicochemically stable. On the contrary, traces of crystalline {LAFT} not observed in the extrudates according to differential scanning calorimetry (DSC), X-ray diffraction (XRD), scanning electron microscopy (SEM) and Raman spectroscopy. Raman micro spectrometry had the lowest detection limit of {LAFT} crystals compared with {XRD} and DSC. Atomic Force microscopy (AFM) studies revealed drug- polymer molecular miscibility and surface interaction at micro level. 1H–COSY {NMR} spectroscopy confirmed miscibility and interaction between {LAFT} and Soluplus?, with chemical shift drifting and line broadening. {MD} simulation studies using computational modelling showed intermolecular interaction between molecules. Dissolution rate and solubility of {LAFT} was enhanced remarkably in developed {SD} systems. Optimized ratio of polymer and surfactants played crucial role in dissolution rate enhancement of {LAFT} SD. The obtained results suggested that developed {LAFT} has promising potential for oral delivery and might be an efficacious approach for enhancing the therapeutic potential of LAFT.