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Iran J of basic med sci 14(4): 383-390. 27. Meier MM, Kanis LA, Soldi V (2004) Characterization and drug-permeation profiles of microporous and dense cellulose acetate membranes: influence of plasticizer and pore forming agent. Int J Pharm 278(1): 99-110. 28. Avachat AM, Bornare PN, Dash RR (2011) Sustained release microspheres of ropinirole hydrochloride:https://doi.org/https://cutt.ly/Zr34WPnMSA Google ScholarThe aim of this study was to prepare sustained release multiple unit dosage form (MUDF) for the oral day delivery of the frequently administered and the highly water soluble drug, dexketoprofen trometamol (DT). The drug was encapsulated into Eudragit RS100 microspheres using emulsification solvent evaporation technique. A D-optimal design was used to determine the effect of amount of polymer (X1), the percentage of hydrophobic plasticizer (X2), the percentage of hydrophilic plasticizer (X3), and stirring rate (X4), on the % entrapment efficiency (Y1), amount of drug released at 1h (Y2), 4h (Y3), and 8 h (Y4). The optimized formulation was prepared using 1.39 g Eudragit, 0.063 g Dibutyl phthalate (DBP), 0.093 g Polyethylene Glycol 400 (PEG 400) and processed using stirring rate of 683 rpm. The optimized microspheres were evaluated by Scanning Electron Microscopy (SEM), Differential Scanning Calorimetry (DSC), and X- ray Diffraction (XRD). Results of the optimized formula showed that the microspheres were spherical with a rough surface and a particle size of 32±1.41 µm, with entrapment efficiency 76.0±1.76%. The amount of drug released was 33.7±0.82%, 60.2±0.05%, and 75.1±1.84%, at 1, 4, and 8 h, respectively. Complete drug release was achieved after 16 h. The sustained release pattern of DT for up to 16 h with an acceptable initial release suggests that the developed MUDF may be useful for oral day delivery of the highly soluble and frequently administered drug such as DTenMultiple Unit Dosage FormDifferential Scanning CalorimetryScanning Electron MicroscopyDexketoprofen TrometamolX-ray DiffractionArticlehttps://doi.org/