Determination of octanol-water partition coefficients of Alkaloids from glycosmis pentaphylla (Retz) DC and formulation of topical creams

Abstract

Glycosmis pentaphylla (Retz) DC contains anti-microbial alkaloids, known as arborine and arborinine. Both of the alkaloids were obtained from bioassay-guided isolation from the crude extract of the leaves. Arborinine, which is non-polar alkaloids can be isolated by using dichloromethane: hexane 80:20 – 95:5, 100% dichloromethane, dichloromethane: ethyl acetate 95:5 – 55:45, giving bright yellow and fine needle- like structure. Combinations of medium and polar solvents dichloromethane: acetone (82: 18 to 70:30 and 45: 55 to 40:60) yielded arborine in the form of white crystal structure. Octanol-water partition coefficients (POW) of arborine and arborinine were determined by the shake-flask method. Each compound was dissolved in octanol to a known concentration and placed in octanol-water system and allowed to equilibrate for at least 72 hours. The octanol-water partition coefficients were determined at varied temperatures (298.15, 303.15, 308.15 and 313.15 K ), in different solvents, at various concentrations and in the presence of non-ionic surfactants. The concentrations of arborine and arborinine in the octanol phase were then determined using standard calibration curves based on the absorbances measured using UV spectrophotometer. The POW was calculated as the ratio of the concentration in octanol phase to the concentration in aqueous phase. With the addition of cosolvents (methanol and ethanol) and non-ionic surfactants (Tween®20 and Span®20), partition coefficients decreased with increasing temperature (except at 40°C) in the presence of non-ionic surfactants. A concentration of 0.1% of either arborine and arborinine was used in palm olein-in-water emulsion and modified to a cream consistency. The cream from F3 containing 25% palm olein, 1.5% Cremophor A25 and 1.0% sodium CMC showed the most stable cream up to at least nine months (up to date) when kept at room temperature 28°C. The particle size distribution of both cream formulations did not show any change throughout storage suggesting good chemical physical stability.