Diloxanide Furoate在碳水化合物及多元醇溶液中之化學與光化學穩定之研究   全文下載

Chemical and Photochemical Stability Studies on Diloxanide Furoate in Carbohydrates and Polyols Solutions

含蔗糖、葡萄糖、果糖、半乳糖及山梨醇之水溶液對diloxanide furoate （DF） 化學穩定性影響被探討，其條件分別為酸性與鹼性培養基，以及40℃與室溫 （25℃ ± 1，由中央空調系統控制恆溫）。在40℃及鹼性培養基下，以上物質均會加速DF之水解速率。室溫下，不同品牌的蔗糖與葡萄糖對DF的穩定有不利的影響。而DF在下列水溶液中則有相對之穩定表現：果糖、半乳糖、山梨醇及商業化Tang(R) （含糖、緩衝液、穩定劑與人工色素）。在上述碳水化合水溶液中DF最穩定之酸鹼值條件落在pH 4.5以下。β-cyclodextrin （β-CD）與hydroxypropyl β-cyclodextrin （HP-β-CD）對DF之化學與光化學穩定性影響亦被探討。在波長254 nm之石英管中，對胺基苯甲酸 （PABA）、抗壞血酸及Tang(R) 對DF均表現良好的光保護效應。DF在鹼性碳水化合物水溶液中被觀測到的加速水解速率可能是由於親核性反應機制造成，而DF水溶液在PABA、抗壞血酸及Tang(R) 的存在下有光穩定效果，可能是因光譜重疊效應。所有以上的研究均以安定性指標高效液相層析法分析。

The effects of aqueous solutions containing sucrose, glucose, fructose, lactose and sorbitol on the chemical stability of diloxanide furoate (DF) were investigated in acid and alkaline media at 40˚C and room temperature (25˚C ± 1, adjusted through thermostatically controlled central-cooling system). All above compounds accelerated the rate of hydrolysis of DF in alkaline medium at 40˚C. At room temperature, different brands of sucrose and glucose had adverse effects on the stability of DF. On the other hand, DF was relatively stable in fructose, lactose and sorbitol, as well as in a commercially available Tang(R) preparation containing sugar, buffers, stabilizers and artificial colours. The optimum pH range of stability of DF in solutions containing these carbohydrates lies below pH 4.5. The influence of β-cyclodextrin (β-CD) and hydroxypropyl β-cyclodextrin (HP-β-CD) on the chemical and photochemical stability of DF was also investigated. Para-aminobenzoic acid (PABA), ascorbic acid and the Tang(R) preparation showed good photo-protective effect on DF solutions irradiated at 254 nm in quartz cell. The observed accelerated rate of hydrolysis of DF by carbohydrates in alkaline medium is proposed to be due to a nucleophilic reaction mechanism while the photostabilization of DF solutions in the presence of PABA, ascorbic acid and the Tang(R) preparation is proposed to be due to a spectral overlay effect. All above studies were conducted using a stability-indicating HPLC method. 含蔗糖、葡萄糖、果糖、半乳糖及山梨醇之水溶液對diloxanide furoate （DF） 化學穩定性影響被探討，其條件分別為酸性與鹼性培養基，以及40℃與室溫 （25℃ ± 1，由中央空調系統控制恆溫）。在40℃及鹼性培養基下，以上物質均會加速DF之水解速率。室溫下，不同品牌的蔗糖與葡萄糖對DF的穩定有不利的影響。而DF在下列水溶液中則有相對之穩定表現：果糖、半乳糖、山梨醇及商業化Tang(R) （含糖、緩衝液、穩定劑與人工色素）。在上述碳水化合水溶液中DF最穩定之酸鹼值條件落在pH 4.5以下。β-cyclodextrin （β-CD）與hydroxypropyl β-cyclodextrin （HP-β-CD）對DF之化學與光化學穩定性影響亦被探討。在波長254 nm之石英管中，對胺基苯甲酸 （PABA）、抗壞血酸及Tang(R) 對DF均表現良好的光保護效應。DF在鹼性碳水化合物水溶液中被觀測到的加速水解速率可能是由於親核性反應機制造成，而DF水溶液在PABA、抗壞血酸及Tang(R) 的存在下有光穩定效果，可能是因光譜重疊效應。所有以上的研究均以安定性指標高效液相層析法分析。