Experimentally derived Hansen Solubility Parameters to screen formulations for Amorphous Solid Dispersions

The popularity of amorphous solid dispersions (ASDs) has increased significantly in pharmaceutical development over the last three decades because they can improve the poor bioavailability of poorly water-soluble active pharmaceutical ingredients (APIs). This is achieved by dispersing a crystalline API within a polymer matrix, thereby stabilizing the API in its amorphous form, which possesses enhanced solubility. However, this approach can constrain an API’s loading capacity and induce API–polymer interactions that may result in incomplete release of the API from the formulation. 

To increase miscibility between the polymer and API and reduce waste early in the development process, a research team at the University of Georgia New Materials Institute utilized experimentally derived Hansen solubility parameters (HSPs) to predict compatibility between 10 commercially relevant polymers and three active pharmaceutical ingredients (APIs). From these 10 polymers, four were selected for ASD formulation and analysis. In these formulations, the team employed hot-melt extrusion to ensure that API/polymer miscibility, rather than API melting behavior, was the primary factor influencing API dissolution within the polymer melt. 

Previous studies on HSPs from The Locklin Group: 

Hansen Solubility Parameter Guided Development of Furan-2, 5-Dicarboxylate Plasticizers for Poly(3-Hydroxybutyrate-co-3-Hydroxyhexanoate). Journal of Applied Polymer Science, 2025, 0:e57649. 

Experimentally Determined Hansen Solubility Parameters of Biobased and Biodegradable Polyesters. ACS Sustainable Chemistry & Engineering, 12(6), 2386-2393. 

Analyses included API solubility studies, polarized optical microscopy, thermogravimetric analysis, differential scanning calorimetry, X-ray diffractometry, Fourier transform infrared spectroscopy, in vitro dissolution studies, and high-performance liquid chromatography. The team found that specific intermolecular interactions significantly influence dissolution behavior and that experimentally derived HSPs reliably predict ASD miscibility and API loading capacity, enabling the rational design of high-performance ASDs with high API loading. 

“Experimentally Derived Hansen Solubility Parameters as a Screening Tool for the Formulation of Amorphous Solid Dispersions” was published recently in the ACS Omega journal. The study was coauthored by Adaeze R. Osakwe, Mira T. N. Le, and Jessica A. Bramhall, of the Locklin Group; Vladislav V. Klepov, an assistant professor of chemistry in the Department of Chemistry; and Jason J. Locklin, director of the UGA New Materials Institute, and a professor of chemistry, and biochemical engineering. Additionally, the paper acknowledged Sammy Bell, an expert in early phase drug development and an adjunct professor at the New Materials Institute, for “helpful discussions on formulation techniques to improve bioavailability of oral solid dosage forms.” 

—by Leighton Dancy