PREPARATION AND EVALUATION OF FLURBIPROFEN DRY ELIXIR AS A NOVEL DOSAGE FORM USING A SPRAY-DRYING TECHNIQUE

A dry elixir containing drug elixir in wall-forming materials as a novel oral dosage form was developed using the spray-drying technique. Poorly water-soluble flurbiprofen (FP) was used as a model compound. The dry elixir was produced when a solution of water-soluble dextrin and drug dissolved in an ethanol-water cosolvent system was spray-dried. The resulting dry elixir was spherical in shape with a geometric mean diameter of about 13 mu m and small pieces of broken shells adhered to large spherical particles. A cross-sectional view of the dry elixir indicates a large inner cavity containing ethanolic drug solution in the dextrin shell. The ethanol contents in the dry elixir were highly dependent on dextrin concentration and inlet air temperatures. As the dextrin concentration increased, the ethanol contents also increased due to the rapid formation of a semipermeable dextrin membrane at the drying particle surface. The ethanol content in the dry elixir was greatest at an inlet air temperature of 90-100 degrees C. The dissolution rate of FP in the dry elixirs within the first 5 min increased markedly compared to FP fine powder and appeared to be proportional to the ethanol content in the dry elixirs. The C-max and absolute bioavailability of FP powder, well-dispersed FP suspension and FP dry elixir were 14.6, 17.2 and 31.3 mu g/ml; 43.6, 45.1 and 66.5%, respectively. There was no change in the T-max among the three products. Although the effective surface area and dispersability of the well-dispersed FP suspension increased, the AUC(0-6 h) and C-max were not significantly changed compared to FP powder. However, the AUC(0-6 h) and C-max of FP in the dry elixir were increased about 1.5- and 2-fold compared to FP powder. The enhanced bioavailability of FP in the dry elixir resulted from the increased dissolution rates of poorly water-soluble FP in aqueous media as a result of the cosolvent effect of ethanol and rapid dispersion of precipitated FP due to the fast dissolution of the dextrin shell. The current spray-drying technique for the preparation of dry elixir may provide a new approach to the solubilization of poorly water-soluble FP for dosage form design. As a result, it was obvious that the dry elixir might be a useful oral dosage form to improve the dissolution rate and bioavailability of poorly water-soluble FP.