Pharmaceutical Study on Clonixin Argininate

Clonixin Argininate의 약제학적 연구

To increase the bioavailability of clonixin, clonixin argininate was prepared and compared with clonixin by determining solubility, pKa, lipid-water partition coefficient, dissolution rate and in vivo tests. The results are summerized as followings; 1) The solubility of clonixin argininate was increased by 20 times in water, about 1.2 times in pH 1.2 and pH 8.0 buffer solution, and about 1.8 times in pH 6.8 buffer solution compared with that of clonixin. 2) pKa values of clonixin, clonixin lysinate and clonixin argininate were 6.32, 7.20 and 7.45, respectively. 3) The lipid-water partition coefficient of clonixin argininate was increased more than that of the clonixin in n-hexane, carbon tetrachloride, chloroform, methylene chloride, and n-butanol, but the partition coefficient of clonixin was increased more than that of clonixin argininate in benzene/pH 1.2 buffer solution, ether/pH 8.0 buffer solution, and 3-methylbutyl acetate/pH 1.2, pH 8.0 buffer solution. 4) The time required to dissolve 60% $(T_{60%},\;min.)$ of clonixin argininate was about 1.5 min. in water and pH 1.2 buffer solution, and about 5 min. in pH 6.8 buffer solution. $T_{60%}$ of clonixin lysinate was about 1.5 min. in water, about 1.8 min. in pH 6.8 buffer solution, and about 8 min. in pH 1.2 buffer solution. But $T_{60%}$ of clonixin was about 96 min. in pH 6.8 buffer solution, over 2 hours in water and pH 1.2 buffer solution. 5) Anti-inflammatory effect of clonixin argininate was increased more than that of clonixin over 6 hours, and that of clonixin lysinate was followed by lapse of time. 6) Analgesic effect of clonixin argininate was increased by 1.5 times more than that of clonixin and the effect of clonixin argininate was nearly identical with that of clonixin lysinate. 7) The absorption rates (Ka) of clonixin, clonixin lysinate and clonixin argininate were $0.169\;hr^{-1},\;0.652\;hr^{-1}$ and $0.723\;hr^{-1}$ in situ, respectively.