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Cefditoren pivoxil is a bactericidal cephalosporin with low oral bioavailability and short half-life. It is used twice daily, causing patient inconvenience and plasma concentration fluctuations. The present work aimed to design a gastroretentive floating matrix of cefditoren pivoxil after enhancing its solubility by solid dispersion technique. Cefditoren solid dispersions (SDs) were prepared by utilizing polyvinylpyrrolidone (PVP) and poloxamer 188. The resulting SDs enhanced cefditoren pivoxil dissolution rate compared to PM; this may be due to the change in physical properties of drug crystal which is confirmed by thermal analysis. SD prepared by PVP was selected for further consideration to prepare gastro-retentive retentive tablets (GFTs) . 2 3 full factorial designs with eight formulations were prepared to utilize the direct compression method. Hydrophilic or hydrophobic swellable polymers (hydroxypropyl methylcellulose K15M or ethyl acetate, respectively) were used with or without a gas-generating agent such as citric acid and sodium bicarbonate. Precompression and postcompression assessments were carried out for powder mixture and GFTs, respectively. F3 displayed the best-sustained release profile. Furthermore, F3 showed good physical stability upon storage under accelerated conditions (40 o C/75% RH) for 3 months.