• Journal of Pharmaceutical Investigation
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• 제26권1호
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• pp.1-11
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• 1996

Biphenyldimethyldicarboxylate (PMC), which has been used to treat hepatitis, is insoluble in water, therefore it has low bioavailability after oral administration. For the purpose of increasing the dissolution rate of PMC, the physical mixtures and inclusion complexes of PMC and $dimethyl-{\beta}-cyclodextrin\;(DM\;{\beta}CD)\;or\;hydroxypropyl-{\beta}-cyclodextrin\;(HP{\beta}CD)$ in molar ratio of 1 : 1 and 1 : 2 were prepared by solvent evaporation method. Mixed micelles of PMC were prepared by reacting PMC with bile salts [sodium cholate(NaC), sodium glycocholate (NaGC)] and oleic acid (OA) or palmitoylcarnitine chloride(PCC). Chloroform/water partition coefficient (PC) of PMC was 36.14 in artificial gastric juice (AGJ) and 33.47 in artificial intestinal juice (AIJ), respectively, on the other hand octanol/water PC was 63.36. PMC formulation was prepared by reacting PMC with PEG400-glycerin system(95 : 5, 90 : 10, respectively) and PEG400-PEG4000-glycerin system (70 : 25 : 5, 65 : 25 : 10, respectively). Dissolution test was performed in AGJ and AIJ by paddle method at $37{\pm}0.5^{\circ}C$. The dissolution rates of PMC tablets on the market were 5.74% and 8.26% at AGJ and AIJ, respectively and marketed PMC capsules were 22.14% and 28.64% at AGJ and AIJ, respectively. The dissolution rates of inclusion complexes of PMC with $DM{\beta}CD$ and $HP{\beta}CD$ in a molar ratio of 1 : 1 were more fast than those of corresponding physical mixtures. The decreasing order of dissolution rates was as follows; PMC-PEG400-PEG4000-glycerin formulation > PMC-PEG400-glycerin formulation > mixed micelles > CD inclusion complexes. The dissolution rates of PMC-PEG400-glycerin and PMC-PEG400-PEG4000-glycerin formulation were most fast and the percentage of dissolution was almost 100% within 20 minutes. And their dissolution rates after 120 minutes were markedly increased as compared with capsules on the market (4.0-fold and 3.2-fold in PMC-PEG400-glycerin formulation at AGJ and AIJ, respectively, and 4.8-fold and 3.7-fold in PMC-PEG400-PEG4000-glycerin formulation at AGJ and AIJ, respectively).