Millisecond Self-Assembly of Stable Nanodispersed Drug Formulations

Vikram J. Pansare, Aditya Rawal, Aaron Goodwin, Ron Beyerinck, Robert K. Prud'Homme, Dwayne T. Friesen, Michael Grass, Annie Muske-Dukes, David T. Vodak

Research output: Contribution to journalArticlepeer-review

3 Scopus citations


We report the development of a new spray-drying and nanoparticle assembly process (SNAP) that enables the formation of stable, yet rapidly dissolving, sub-200 nm nanocrystalline particles within a high T g glassy matrix. SNAP expands the class of drugs that spray-dried dispersion (SDD) processing can address to encompass highly crystalline, but modestly hydrophobic, drugs that are difficult to process by conventional SDD. The process integrates rapid precipitation and spray-drying within a custom designed nozzle to produce high supersaturations and precipitation of the drug and high T g glassy polymer. Keeping the time between precipitation and drying to tens of milliseconds allows for kinetic trapping of drug nanocrystals in the polymer matrix. Powder X-ray diffraction, solid state 2D NMR, and SEM imaging shows that adding an amphiphilic block copolymer (BCP) to the solvent gives essentially complete crystallization of the active pharmaceutical ingredient (API) with sub-200 nm domains. In contrast, the absence of the block copolymer results in the API being partially dispersed in the matrix as an amorphous phase, which can be sensitive to changes in bioavailability over time. Quantification of the API-excipient interactions by 2D 13 C- 1 H NMR correlation spectroscopy shows that the mechanism of enhanced nanocrystal formation is not due to interactions between the drug and the BCP, but rather the BCP masks interactions between the drug and hydrophobic regions of the matrix polymers. BCP-facilitated SNAP samples show improved stability during aging studies and rapid dissolution and release of API in vitro.

Original languageEnglish (US)
Pages (from-to)495-507
Number of pages13
JournalMolecular Pharmaceutics
Issue number2
StatePublished - Feb 5 2018

All Science Journal Classification (ASJC) codes

  • Drug Discovery
  • Molecular Medicine
  • Pharmaceutical Science


  • 2D NMR
  • nanocrystals
  • nanoparticle
  • phenytoin
  • solid state NMR
  • solubility enhancement
  • spray-drying


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