Formulation Optimization of the Tablet Prepared with Solid Dispersion of Biphenyl Dimethyl Dicarboxylate with Poloxamer

비페닐 디메칠 디카르복실레이트 고체분산체 정제 처방의 최적화

Biphenyl dimethyl dicarboxylate (DDB) has been used for the treatment of acute and chronic hepatitis. However, its poor solubility in water, $2.5\;{\mu}g/ml$, caused low bioavailability of the drug after its oral administration. In order to increase the dissolution of DDB in gastrointestinal tracts, consequently to increase the bioavailability of the drug, DDB tablet was prepared with solid dispersion of DDB with poloxamer 338 or 407 using a direct compression method. To improve the flowability of the solid dispersion, Aerosil was used as an adsorbent. The effect of formulation variables (poloxamer and Aerosil contents) on the dissolution rate of DDB from tablets was investigated using an analysis of variance. The dissolution rate of DDB from tablets was evaluated with KP II (paddle) method. The dissolution patterns of the drug from the tablet prepared with poloxamer 407 were affected significantly by the contents of poloxamers and Aerosil over the range employed, but those of the drug from the tablet prepared with poloxamer 338 were not. The optimum formulation of the DDB tablet, showed the same dissolution pattern as that of the reference, was obtained after polynomial equations of drug dissolution profiles for each formula were fitted to contour plots. The optimum formulation ratios of DDB:poloxamer 407:Aerosil were 1:2.5:2.5 and 1:5:5.