Evaluation of the impact of the dialysis setup used on the in vitro dissolution behaviour of parenteral drug suspensions.

Long-acting injectable (LAI) parenteral formulations are becoming increasingly important in drug therapy. Therefore, reliable and discriminatory in vitro dissolution methods are needed to support formulation development and the selection of promising candidate formulations before clinical studies. In this study, triamcinolone acetonide suspensions were used as a model system to investigate how different experimental parameters influence dissolution behaviour in dialysis-membrane based setups. Drug suspensions were placed in dialysis adapters enclosed in regenerated cellulose membranes. The adapters were integrated into compendial dissolution systems (USP apparatus 1 and 2). The influence of adapter orientation, agitation, adapter size, and membrane molecular weight cut-off (MWCO) was systematically investigated. Adapter orientations were first compared under constant MWCO conditions. The effect of rotational speed was then studied separately for horizontal and vertical orientations. Adapters of different sizes were compared at constant MWCO, and membranes with different nominal MWCOs were evaluated for both orientations. The results showed that all investigated parameters influenced the dissolution behaviour. The largest differences were observed between the different adapter orientations, indicating that the experimental setup strongly affects the dissolution process. In addition, larger membrane surface areas resulted in faster dissolution, and increasing rotational speed also accelerated dissolution. Membranes with higher MWCO generally led to faster dissolution. Post hoc mathematical approaches were explored to describe the influence of rotational speed and membrane surface area and provided a first approximation of the observed trends. However, the influence of MWCO could not be adequately described. Overall, the results show that several experimental parameters affect dissolution in dialysis-based systems. A clear understanding of the underlying processes is therefore essential to select appropriate models and to develop robust and clinically relevant in vitro dissolution methods for long-acting injectable suspensions.