Recent Advances in Understanding the Micro- and Nanoscale Phenomena of Amorphous Solid Dispersions

Ralm G. Ricarte, Nicholas J. Van Zee, Ziang Li, Lindsay M. Johnson, Timothy P. Lodge, Marc A. Hillmyer

Research output: Contribution to journalArticlepeer-review

49 Scopus citations


Many pharmaceutical drugs in the marketplace and discovery pipeline suffer from poor aqueous solubility, thereby limiting their effectiveness for oral delivery. The use of an amorphous solid dispersion (ASD), a mixture of an active pharmaceutical ingredient and a polymer excipient, greatly enhances the aqueous dissolution performance of a drug without the need for chemical modification. Although this method is versatile and scalable, deficient understanding of the interactions between drugs and polymers inhibits ASD rational design. This current Review details recent progress in understanding the mechanisms that control ASD performance. In the solid-state, the use of high-resolution theoretical, computational, and experimental tools resolved the influence of drug/polymer phase behavior and dynamics on stability during storage. During dissolution in aqueous media, novel characterization methods revealed that ASDs can form complex nanostructures, which maintain and improve supersaturation of the drug. The studies discussed here illustrate that nanoscale phenomena, which have been directly observed and quantified, strongly affect the stability and bioavailability of ASD systems, and provide a promising direction for optimizing drug/polymer formulations.

Original languageEnglish (US)
Pages (from-to)4089-4103
Number of pages15
JournalMolecular pharmaceutics
Issue number10
StatePublished - May 31 2019

Bibliographical note

Publisher Copyright:
© 2019 American Chemical Society.


  • amorphous solid dispersions
  • drug-polymer interactions
  • solubility enhancement


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