Amorphous nanopharmaceuticals (NP) have emerged as a highly effective bioavailability enhancement formulation strategy of poorly soluble drugs owed to their supersaturation generation capability. Spray drying, which is regularly employed in solid dosage form preparation of amorphous NP, adversely affects the supersaturation generation. The adverse effect is caused by the high crystallization propensity of the spray-dried products resulted from poor disassociation of the spray-dried nanoparticle aggregates. Herein, we developed adjuvant formulations to mitigate the adverse effect of spray drying on the supersaturation generation capability of amorphous NP. Two types of water-soluble adjuvants were investigated, i.e., (1) fast-dissolving mannitol and trehalose and (2) crystallization inhibiting hydroxypropylmethylcellulose (HPMC). The supersaturation generation was evaluated in terms of the area under the curve (AUC) of the supersaturation versus time plot. The results showed that co-spray drying of amorphous NP with two adjuvant types were mandatory to have a prolonged supersaturation profile, which significantly improved the AUC (approximate to 70% larger) compared to spray drying without adjuvants. Using only one adjuvant type resulted in either stagnant or high yet short-lived supersaturation profiles manifested in less than 20% improvement in the AUC. Furthermore, physically mixing the two adjuvant types (instead of co-spray drying) led to inferior supersaturation generation. Thus, adjuvant formulations targeted only at effective disassociation of the nanopartide aggregates were ineffective if the improved supersaturation generation rate was not accompanied by crystallization inhibition of both the supersaturated solution and the remaining solid phase. (C) 2015 Elsevier B.V. All rights reserved.