The AMF exposure time was not a significant factor for drug amorphization in the selected design space; however, the model term for the duration of AMF was retained to improve the predictability of the model. The contour plot for tablets containing Zn ferrite (Figure ) indicate that the tablets that failed to reach the onset temperature (Table ) show minimal amorphization despite prolonged AMF exposure. Thus, a minimum AMF exposure time of three minutes was selected to ensure at least some degree of drug amorphization. As a result, the AMF exposure time is a non-significant factor in the current model. In future studies, the effect of time on hyperthermia-induced drug amorphization could be investigated by increasing the range and interval of the design. As previously discussed, heating efficiency of SPIONs depends strongly on the operating AMF amplitude. The maximum AMF amplitude used in this study was confined due to the instrument limitations, however using higher AMF amplitude could potentially decrease the time required for AMF exposure and the SPION content required to achieve complete amorphization. Nanoparticle Cytotoxicity on Caco-2 Cells. The most effective hyperthermia-induced drug amorphization was achieved using the Mn0.5Fe2.5O4 nanoparticles (Figure ). However, the final choice of an enabling excipient for in situ drug amorphization must also be guided by the potential toxicity of the nanomaterial. Figure shows the dose-dependent viability of human intestinal Caco-2 cells following 24 hours of exposure to the SPIONs. Cell viability after nanoparticle exposure is highly dependent on cell line and differentiation state, exposure time and concentration, and physicochemical properties of the nanoparticles. Here, cell viability was assessed using non-differentiated cells, which are more sensitive than differentiated ones. In other words, our model is highly sensitive compared to the in vivo condition, and better able to detect any toxic effects exhibited by the flame-made SPIONs. The cell viability was not affected by γ-Fe2O3 and Mn0.5Fe2.5O4 exposure at 100 μg mL -1 (corresponding to an oral dose of 25 mg SPIONs ingested with a 250 mL glass of water) and was only slightly decreased at higher concentrations. This declining trend of cell viability with increasing particle concentration (Figure ), suggests a dose-dependent toxicity for all particles. The minor adverse effect of iron oxide nanoparticles on Caco-2 cell viability has also previously been reported. In contrast, Zn0.5Fe2.5O4 dramatically reduced cell viability to 75% compared to the control already after exposure to 100 μg mL -1 and further to 63% at 200 μg mL -1 . Mn0.5Fe2.5O4 on the other hand shows significantly higher cell viability than zinc ferrite. Previous studies have also reported relatively higher cytotoxicity of zinc ferrite compared to manganese ferrite, which can be attributed to the oxidative stress induced by generation of reactive oxygen species by the former. Overall, the high heating efficiency and low cytotoxicity of the Mn0.5Fe2.5O4 nanoparticles suggest they are efficient as enabling excipients for hyperthermia-induced in situ amorphization. In Vitro Dissolution Studies. In vitro dissolution assays of celecoxib ASDs in biorelevant intestinal media under non-sink conditions have previously shown good correlation with their in vivo performance. We therefore used them to benchmark the in situ amorphized ASD. Figure shows the in vitro dissolution profiles of crystalline celecoxib, amorphous celecoxib, conventional ASD (prepared by melt quenching) and tablets containing Mn0.5Fe2.5O4, before and after magnetic hyperthermia-induced amorphization. The conventional ASD showed a considerably higher dissolution rate and maximum drug concentration (Cmax) than pure crystalline or amorphous celecoxib. This is in good agreement with previous studies demonstrating the superior dissolution characteristics of ASDs compared to pure compounds. The dissolution profile of ASDs are mainly controlled by generation and stabilization of a supersaturated solution, this is commonly referred to as the 'spring and parachute effect', and suggests that the performance of an ASD is governed by the dissolution rate and crystallization inhibition of the polymer. PVP maintains the balance between the dissolution rate enhancement and precipitation inhibition. The tablets containing Mn ferrites achieved a similar dissolution profile after AMF exposure as the conventional ASD, reaching a Cmax of 239 μg mL -1 in 15 min. This concentration was significantly higher than Cmax of conventional ASD (215 μg mL -1 ) and approximately five times higher than the Cmax of the SPION-containing tablets before AMF exposure (46 μg mL -1 ). At the end of sampling period (6 hours), the AMF-exposed tablets maintained a higher solubility compared to the conventional ASD and the crystalline celecoxib (Figure ). The presence of crystalline nanoparticles in the formulation could act as a crystalline nuclei and trigger re-crystallization, however Mn ferrites did not trigger re-crystallization, thus further affirming their suitability as an in situ amorphization enabling excipient. Overall, this confirms that the novel magnetic hyperthermia-induced amorphization produces ASDs with the same performance as conventional ASDs in terms of their dissolution behavior.