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Amorphous solid dispersion (ASD) is an enabling approach utilized to deliver poorly soluble compounds. ASDs can spontaneously generate drug-rich amorphous nanoparticles upon dissolution, which can act as a reservoir for maintaining supersaturation during oral absorption. But, conventional ASDs are often limited in drug loadings to < 20 %. For indications where the dose is high, this can translate into a significant pill burden. The aim of this research was to develop a high drug loading (DL) amorphous nanoparticle (ANP) formulation that can release the drug-rich nanoparticles into solution upon contact with aqueous environment. Nanoparticles were directly engineered using solvent/anti-solvent precipitation. The obtained nanoparticle suspension was then concentrated followed by solidification to a re-dispersible amorphous dosage form using spray drying or lyophilization. The impact of process variables was studied using dynamic light scattering (DLS), scanning electron microscopy (SEM), high performance liquid chromatography (HPLC), nuclear magnetic resonance (NMR) and differential scanning calorimetry (DSC). It was observed that spray drying led to a non-re-dispersible formulation. Sucrose and trehalose containing lyocakes resulted in re-dispersible formulations. The trehalose containing lyocakes, in a dog study, gave comparable performance to the reference tablet in the fasted state but lower area under the curve (AUC) in fed state., Competing Interests: Declaration of Competing Interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: AbbVie sponsored and funded the study; contributed to the design; participated in collection, analysis, and interpretation of data; and in writing, reviewing, and approval of the final version. Hitesh S. Purohit, Mengqi Yu, Hardeep Oberoi, Angélica de L Rodríguez López, Manish Kelkar, Yan He, Bradley Gates, Nandkishor Nere, Devalina Law are AbbVie employees and may own AbbVie stock. Maryam Zaroudi contributed to the research during her summer internship at AbbVie. Deliang Zhou contributed to the research during his employment at AbbVie., (Copyright © 2023 American Pharmacists Association. Published by Elsevier Inc. All rights reserved.)