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

作　　者：Ritesh Fule Purnima Amin 

机构地区：[1]Department of Pharmaceutical Sciences and Technology,Institute of Chemical Technology,Nathalal Parekh Marg,Matunga,Mumbai 400019,Maharashtra,India

出　　处：《Asian Journal of Pharmaceutical Sciences》2014年第2期92-106,共15页亚洲药物制剂科学（英文）

基　　金：The author is also thankful to UGC(SAP)for providing the research fellowship and Institute of Chemical Technology,ELITE status(Mumbai,India)for providing all facilities and guidance.The authors are thankful to S.A.I.F.department at Indian Institute of Technology,Mumbai for Raman and 1HeCOSY NMR experimental help and analyses.

摘　　要：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 drugpolymer molecular miscibility and surface interaction at micro level.1HeCOSY 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.

关 键 词：LAFUTIDINE Solid dispersion Hot melt extrusion Dissolution rate Raman spectroscopy Atomic force microscopy 

分 类 号：O63[理学—高分子化学]