Overcoming Bioavailability Challenges of Very Weak Acid for Oral Delivery – A Case Study of HCV Drug Dasabuvir

26 September 2022 16:30 - 17:00

  • Dasabuvir is a BCS II compound posing a significant barrier to achieving sufficient human bioavailability. Its substantially weak acidity (pKa > 8) made salt approach challenging and risky due to disproportionation.
  • Identification of effective crystallization inhibitors captured the dissolution advantage of dasabuvir sodium salt and provided a path forward for formulation development.
  • The comprehensive evaluation of solid-state properties, biopharmaceutical properties, in-vivo pharmacokinetics, and manufacturability of dasabuvir monosodium monohydrate ensured the selection of this solid form for successful formulation development and clinical studies.
  • Oral delivery of dasabuvir via salt approach ultimately helped enable the triple combination direct acting antiviral HCV regimen Viekira Pak.

Shuang Chen, Ph.D., Sr. Principal Research Scientist Solid State Chemistry, Process R&D, AbbVie