Nanoparticle Properties. Zinc and manganese ferrites were prepared by flame spray pyrolysis (FSP) and investigated as enabling excipients for in situ amorphization in tablets containing celecoxib. Flame process parameters were set to produce nanoparticles with primary particle sizes in the range of 12-20 nm. This size range has been reported, both experimentally and computationally, to result in maximum heating efficiency during hyperthermia. Table summarizes nanoparticle size, magnetization, and heating efficiency in an AMF of as-produced SPION powders. Pure iron oxide is included for comparison. Figure shows the X-ray diffraction (XRD) patterns of pure γ-Fe2O3 and SPION doped with Zn 2+ and Mn 2+ to form the ferrites, Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4. The diffractograms correspond to spinel cubic structures, exhibiting six prominent peaks originating from the (220), (311), (400), (422), (511) and (440) crystallographic planes. Pure iron oxide forms γ-Fe2O3 (maghemite), in agreement with previous SPION synthesis in oxygen-rich flames. Spinel-ferrite structures were formed by the addition of Zn 2+ or Mn 2+ , as evidenced by a slight shift of diffraction peaks towards lower angles (shown in Figure as the dashed line at the (311) plane). The peak shift is accompanied with a lattice expansion (Table ), indicating the successful incorporation of Zn and Mn 2+ ions into the γ-Fe2O3 crystal lattice. Furthermore, no diffraction peaks corresponding to pure zinc oxide or manganese oxide were observed. The average crystallite size (dXRD) was about 14 nm for both γ-Fe2O3 and Zn0.5Fe2.5O4 and 18 nm for Mn0.5Fe2.5O4 (Figure ). The larger ionic radius of Mn 2+ (0.81 Å) compared to Fe 3+ (0.64 Å) and Zn 2+ (0.74 Å) at the tetrahedral site might explain the increase in crystal size for the manganese ferrite. Figure and 2c show representative transmission electron microscopy (TEM) images of Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4 nanoparticles, respectively. The nanoparticles are polyhedrons with a narrow primary particle size distribution (Figure ) in excellent agreement with the literature. The primary particle size determined from TEM analysis (dTEM) was about 18 nm for both ferrites, in good agreement with the dXRD and thus suggesting primarily monocrystalline particles. The dTEM also falls within the targeted optimal range of SPION particle size (12-20 nm) for high heating rates. The geometric standard deviation (σg) was 1.48 and 1.52 for Zn0.5Fe2.5O4 and Mn0.5Fe2.5O4, respectively, and thus corresponds to the theoretical self-preserving size distribution that is typically attained during flame synthesis. 39 Magnetic Properties and Heating Efficiency. Figure shows the magnetization of flamemade SPIONs. The nanoparticles exhibit nearly zero hysteresis confirming their superparamagnetism. At the maximum field of 1000 mT, nearly all particles reached their saturation magnetization. Bulk maghemite has a saturation magnetization of 80 emu g -1 , which is considerably higher than the 53.7 emu g -1 measured for γ-Fe2O3 here (Table ). This can be attributed to the small particle size that increases the thickness of the surface spin disordered layer, also called the "magnetically dead layer". Mn0.5Fe2.5O4 exhibits the highest saturation magnetization (66.7 emu g -1 ) of the flame-made SPIONs here, in agreement with the literature. The dopant occupies the tetrahedral or octahedral sites in the structure of γ-Fe2O3, which affects the magnetocrystalline anisotropy and increases the overall magnetic moment of the unit cell, thereby also affecting the saturation magnetization of the SPIONs. Surprisingly, the incorporation of Zn 2+ in γ-Fe2O3 did not enhance the saturation magnetization in contrast to previous reports. This could be due to the smaller size of the zinc ferrite compared to manganese ferrite and hence the increased relative volume contribution of the magnetically dead layer to the total particle volume for the former. Moreover, the high substitution of Fe 3+ ions by Zn 2+ ions at the tetrahedral site also weakens the exchange coupling between the tetrahedral and octahedral sites, thus decreasing the total magnetic moment of the unit cell. Figure shows the heating efficiency (represented as the temperature increase ΔT after 10 seconds) of the nanoparticle powders in an AMF. The heating efficiency was directly measured on the bulk powders (in contrast to how particle suspensions are typically measured) as they were used here in their dry state in the final tablet formulations, hence the heat dissipation is primarily originating from Néel relaxation of the SPIONs. The zinc, and especially the manganese ferrite, both generated significantly higher temperatures than γ-Fe2O3, in agreement with previous reports. Heating efficiency of SPIONs is often correlated with the saturation magnetization, and this was especially obvious for Mn0.5Fe2.5O4 (Figure ). Furthermore, the heating efficiency increased with increasing magnetic field amplitude, also in agreement with previous studies. Overall, these results demonstrate the superior heating efficiency of Zn and Mn ferrites compared to γ-Fe2O3. We therefore investigated these two ferrites further for the magnetic hyperthermia-induced in situ amorphization. ). b) IR images captured at four time points (i: 0 min, ii: 0.5 min, iii: 1 min, iv: 6 min). The color scale indicates the temperature of the tablet. c) XRD diffractograms and d) DSC thermograms of tablets containing 30 wt% celecoxib and 20 wt% Mn0.5Fe2.5O4 before and after 3 and 15 minutes of AMF exposure time.