The tangential flow absorption model (TFAM) - A novel dissolution method for evaluating the performance of amorphous solid dispersions of poorly water-soluble actives.

There is a substantial demand for absorptive dissolution tests, as single vessel dissolution experiments were originally not designed for testing supersaturating systems. Current approaches suffer from inadequate mass transfer of the dissolved active from the dissolution site, discrepancies in the fluid volume compared to in vivo intestinal fluid volumes or the dilution of functional excipients. In this work a novel dissolution apparatus was developed that enables adjustable mass transfer of the active through a membrane, while retaining the functional polymeric excipients at the dissolution site. Using this setup the dissolution behavior of various spray dried amorphous solid dispersions containing carbamazepine, hydrochlorothiazide and ketoconazole as model actives at intermediate and high supersaturation levels was evaluated. Compared to non-absorptive dissolution experiments, differences in the concentration-time profiles were noted. The experiments with a high supersaturation of ketoconazole revealed a concentration decrease over time under absorptive conditions. Additionally, it was observed that the difference between "spring" as well as "spring and parachute" formulations was less pronounced with increasing drug efflux. Further, the apparatus was also tested with Fasted State Simulated Intestinal Fluid as dissolution medium and results were compared to phosphate buffer pH6.8. As major benefits of the new TFAM apparatus the easy experimental procedure and sample preparation for drug concentration measurements using spectroscopy in the permeate, without the necessity for additional filtration and/or centrifugation to remove precipitated drug molecules, could be highlighted. This TFAM approach seems to be a promising tool for identifying formulations for amorphous solid dispersions with optimal in vitro performance.