| Summary: | The present study evaluates the crystal growth rate of amorphous drugs when dispersed in different ternary polymeric amorphous solid dispersions (ASDs) in the presence of surfactants. Specifically, ternary ASDs of aprepitant (APT, selected as a model drug) were prepared via melt-quench cooling by evaluating three commonly used ASDs matrix/carriers, namely hydroxypropyl cellulose (HPC), poly(vinylpyrrolidone) (PVP) and the copolymer Soluplus® (SOL), and two suitable surfactants, namely d-alpha tocopheryl polyethylene glycol 1000 succinate (TPGS) and poly(ethylene glycol)-block-poly(propylene glycol)-block-poly(ethylene glycol) (P407). Results showed that all components were completely miscible (verified via hot stage polarized microscopy) and both surfactants were acting as plasticizers to the API. APT's crystal growth rate was increased in the presence of both P407 and TPGS, while PVP was identified as the matrix/carrier with the greatest impact API's crystal growth rate inhibition. Interestingly, TPGS presented a noticeable synergistic effect when combined with PVP resulting in a further reduction of APT's crystal growth rate. Furthermore, evaluation of APT's nucleation induction time in dissolution medium (PBS pH 6.8) revealed PVP as the most effective crystallization inhibitor, whereas the addition of TPGS showed to improve PVP's ability to inhibit APT's recrystallization. Finally, the formation of intermolecular interactions in the ternary APT-PVP-TPGS provided an explanation for the observed PVP-TPGS synergistic effects, with molecular dynamics simulations being able to unravel the type and extent of these interactions on a theoretical basis.
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