Supersaturated dissolution data and their interpretation: the TPGS–carbamazepine model case

Abstract

Abstract Objectives This study was undertaken to investigate the effect of d-alpha-tocopheryl polyethylene glycol 1000 succinate (vitamin E TPGS) on the dissolution of carbamazepine (CBZ) commercial tablets (Tegretol®) as a function of temperature and to modify the reaction-limited model of dissolution for the description of classical supersaturated dissolution data. Methods Solubility studies were performed using various concentrations of (i) TPGS and (ii) silicon dioxide and microcrystalline cellulose, which are excipients of Tegretol® at 10, 25 and 37°C. Dissolution studies were carried out using Tegretol® tablets, 200 mg/tab. Key findings The solubility of CBZ in the presence of TPGS was found to increase in a concentration-dependent manner at all temperatures studied. Classical supersaturated dissolution curves with concentration maxima higher than the corresponding solubility values in the presence of TPGS were observed only at 10°C. The model developed was based on a time-dependant expression for the forward microconstant of the CBZ-TPGS reaction at the solid–liquid interface and it was fitted successfully to the dissolution data of CBZ in the presence of TPGS at 10°C. Conclusions Vitamin E TPGS increased the solubility of CBZ at all temperatures studied. The modification of the reaction-limited model of dissolution allowed us to describe classical supersaturated dissolution curves.