The kinetics of the hydrolysis of the oleate ester of polyoxyethylene (20) sorbitan (Tween 80) in aqueous buffers were studied at an initial concentration of0.020% (w/v) and over the pH range of 1.10 to 10.28. The hydrolysis appears to be specific acid-catalysed at pH va!ues below 3 and specific base-catalysed at pH values greater than 7.6. The pseudo first-order rate constants for hydrogen and hydroxyl ion catalysis were determined, and the temperature and ionic strength dependence of the acid-catalysed reaction was studied. Both the initial, acid-and base-catalysed hydrolysis of Tween 80 exhibited an unusual initial, micellar surfactant concentration-rate dependence, opposite to that previously reported for the hydrolysis of anionic surfactants of the n-alkyl sulphate-type. Specifically, as the initial concentration of Tween 80 was increased above its reported critical micellar concentration, there was a progressive, marked decrease in the rate of the reaction, with the rate eventually reaching a plateau value between 0.100 and 1.00% (w/v); It is suggested that this behaviour is due to alterations in the micellar state of the surfactant as its concentration is increased. The influence of the chemical structure of the Tween surfactant on the acid-catalysed hydrolysis reaction at 80" was also examined using the oleate (Tween 80), stearate (Tween 60), and palmitate (Tween 40) esters of polyoxyethylene (20) sorbitan.Tweens are non-ionic surface-active mono-fatty acid esters of polyoxyethylene sorbitan, usually containing approximately 20 moles of ethylene oxide. Because of their high surface activity and relatively low toxicity, they have been used as solubilizers, wetting agents, and emulsifiers in pharmaceuticals. However, their ability to function effectively in these products depends on the chemical stability of the ester linkage of the monomer.There is a paucity of quantitative information on the degradation kinetics of nonionic surfactants of the Tween-type (Aoki, Hiroshi & Ise, 1968). We have examined the kinetics of hydrolysis of some esters of polyoxyethylene sorbitan. MATERIALS A N D METHODS MaterialsPolyoxyethylene (20) sorbitan mono-oleate (Tween 80), mono-stearate (Tween 60), and mono-palmitate (Tween 40) were supplied by the Atlas Powder Company (Wilmington, Del., U.S.A.) and were used as received. All other chemicals were of reagent grade quality.

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The effect of food on the absorption of five commercial dosage forms of nitrofurantoin varying widely in drug release and dissolution characteristics was assessed in man after oral administration. Four healthy fasting and nonfasting male subjects received, in a crossover fashion, a single 100-mg dose of microcrystalline nitrofurantoin as an aqueous suspension, three different compressed tablets, and a single 100-mg dose of macrocrystalline nitrofurantoin in a capsule. Both the absorption and the duration of therapeutic urinary concentrations of nitrofurantoin were significantly increased after administration of the five products to nonfasting subjects. The enhancement in the bioavailability of the drug in the presence of food ranged from 20% to 400%, with the greatest absorption-enhancing effect occurring with those dosage forms exhibiting the poorest dissolution characteristics. It is concluded that single-dose comparative bioavailability studies of drug products normally administered with food should be performed in both nonfasting and fasting subjects.

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