Absorption studies of albendazole and some physicochemical properties of the drug and its metabolite albendazole sulphoxide

Abstract

In several studies of patients with neurocysticercosis under treatment with albendazole the pharmacokinetic data were difficult to interpret, probably because of slow and erratic drug dissolution response and absorption problems in-vivo. Because there is no information available about the physicochemical properties of the drug, the aim of this work was to explain this erratic behaviour by fully characterizing the solution behaviour of the drug and its metabolite. To accomplish this, the physicochemical properties, pK(a) and solubility, and in-vitro plasma binding of albendazole and its main metabolite, albendazole sulphoxide, were studied by conventional methods. The intestinal and gastric absorption and dissolution behaviour of albendazole were also studied. The solubility of both compounds is very low. Both are amphoteric molecules with two ionization steps, with pK(a) values of 10.26 and 2.80 for albendazole and 9.79 and 0.20 for albendazole sulphoxide; low pK(a) values were obtained by performing linear free energy relationship calculations. On the other hand, protein binding studies showed that albendazole is 89-92% bound to plasma proteins whereas for albendazole sulphoxide the figure is 62-67%. This metabolite is bound by albumin and to α1-glycoprotein. Absorption of albendazole occurs along the gastrointestinal tract and is limited by its solubility. Good dissolution profiles were observed when 0.1 M HCl was used as dissolution medium. The results show that 0.1 M HCl enables discrimination between the drug-release characteristics of different products.