Chemical and photochemical stability studies on diloxanide furoate in carbohydrates and polyols solutions

Abstract

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® 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® 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® preparation is proposed to be due to a spectral overlay effect. All above studies were conducted using a stability-indicating HPLC method.