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논문 기본 정보
- 자료유형
- 학술저널
- 저자정보
- 저널정보
- 한국응용약물학회 The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology The journal of applied pharmacology : the official journal of the Korean Society of Applied Pharmacology 제4권 제4호
- 발행연도
- 1996.1
- 수록면
- 419 - 427 (9page)
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To solubilize practically insoluble biphenyl dimethyl dicarboxylate (DDB), which has been used for the treatment of chronic hepatitis as tablets or hard capsules, the solubilities of DDB in various hydrophilic, oily and hydrocarbon vehicles, and aqueous surfactant solutions were measured by high performance liquid chromatography. It was found that, among the vehicles studied, polyethylene glycol (PEG) 300 revealed the best solvency, and the solubility reached 17.6 mg/ml at 37$^{\circ}C$. The addition of glycyrrhizic acid ammonium salt (GAA) to DDB-PEG 300 solution (5-20 mg/g) inhibited the formation of precipitates, and at the concentration of 10 mg/g, any precipitaction was not observed even after 2 years at 4$^{\circ}C$. Furthermore, GAA markedly enhanced the permeation of DDB through the rabbit duodenal mucosa in a concentration dependent manner. The addition of copolyvidone (ca. 1.0%) to DDB-GAA-PEG 300 system (1 : 0.5 97.5 w/w) was most effective in preventing the considerable precipitation of DDB-PEG 300 solution (7.5 mg/750 mg) when mixed with water of 300-900 ml at 37$^{\circ}C$. GAA showed a synergistic effect in the prevention of precipitate formation. This finding suggests that this DDB formulation may form less precipitation when DDB soft capsules disintegrate and diffuse into the gastrointestinal fluid, resulting in improving the bioavailability Dissolution rate of DDB (7.5 mg) from sort elastic capsules of DDB-GAA-PEG 300 system was rapid. The supersaturation state was maintained for 2 hr at the concentration of 7.35$\pm$3.3 mg in 900 ml of water without precipitation. The total amount of DDB dissolved from this new formulation was 5.3 and 6.1 times higher, when compared to marketed DDB tablets (25 mg) and capsules (7.5 mg), respectively.
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