One of the most commonly used formulation development tools is dissolution testing. However, for solubility enhancing formulations, a simple closed compartment conventional dissolution apparatus operating under sink conditions often fails to predict oral bioavailability and differentiate between formulations. Hence, increasing attention is being paid to combined dissolution-absorption testing. The currently available mass transport apparatuses, however, have certain limitations, the most important being the small membrane surface area, which results in slow mass transfer. In this study, a novel high surface area, flow-through absorptive dissolution testing apparatus was developed and tested on a weakly basic model drug, nevirapine. Following optimization of the experimental parameters, the mass transfer attained for a nevirapine solution was 30 times higher in 60 min as compared to a side-by-side diffusion cell. To further evaluate the system, nevirapine powder and commercial tablets were first dissolved at an acidic pH, followed by pH increase, creating a supersaturated solution. Detailed information related to the extent of supersaturation achieved in crystallizing and noncrystallizing systems could be obtained from the combined dissolution-mass transport measurements. Differences in donor cell compartment concentration-time profiles were noted for absorptive versus closed compartment conditions. It is anticipated that this approach could be a promising tool to identify solubility enabling formulations that perform optimally in vivo.

The tendency of highly supersaturated solutions of poorly water-soluble drugs to undergo liquid–liquid phase separation (LLPS) into drug-rich and water-rich phases when the concentration exceeds the amorphous solubility, for example, during dissolution of some amorphous solid dispersions, is thought to be advantageous from a bioavailability enhancement perspective. Recently, we have developed a high surface area, flow-through absorptive dissolution testing apparatus that enables fast mass transfer providing more in vivo relevant conditions and time frames for formulation testing. Using this apparatus, the absorption behaviors of solutions with different extents of supersaturation below and above the amorphous solubility were evaluated. In addition, simultaneous dissolution–absorption testing of amorphous solid dispersions (ASDs) with varying drug loadings and polymer types was carried out to study and distinguish the absorption behavior of ASDs that do or do not undergo LLPS. When compared with closed-compartment dissolution testing, a significant influence of the absorptive compartment on the dissolution rate of ASDs, particularly at high drug loadings, was observed. The formation of drug-rich nanodroplets, generated by both solvent-addition and ASD dissolution, resulted in a higher amount of drug transferred across the membrane. Moreover, the mass transfer was further enhanced with increasing concentration above the amorphous solubility, thereby showing correlation with an increase in the number of drug-rich particles. The importance of including an absorptive compartment in dissolution testing is highlighted in this study, enabling coupling of dissolution to membrane transport, and providing a more meaningful comparison between different formulations.

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