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It is crucial to improve poorly water-soluble orally administered drugs through both preclinical and therapeutic drug discovery. A co-amorphous formulation consisting of two low molecular weight (MW) molecules offers a solubility/dissolubility advantage over its crystalline form by maintaining their amorphous status. Here, we report on a co-amorphous solid dispersion (SD) system that includes inert carriers (lactose monohydrate or microcrystalline cellulose) and co-amorphous sacubitril (SAC)-valsartan (VAL) using the spray drying process. The strong molecular interactions between drugs were the driving force for forming robust co-amorphous SDs. Our system provided the highest solubility with more than ~11.5- and 3.12-times solubility increases when compared with the physical mixtures. Co-amorphous lactose monohydrate (LM) SDs showed better bioavailability of APIs (~356.27.8% and 154.01% for the relative bioavailability of LBQ 657 and valsartan, respectively). Co-amorphous inert carrier SDs possessed an excellent compressibility for the production of a direct compression pharmaceutical product. In conclusion, these brand-new co-amorphous SDs could reduce the number of unit processes to produce a final pharmaceutical product for downstream manufacturability.

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