Stability and intrinsic dissolution of vacuum compression molded amorphous solid dispersions of efavirenz

Jacob Rune Jørgensen, Wolfgang Mohr, Matthias Rischer, Andreas Sauer, Shilpa Mistry, Anette Müllertz*, Thomas Rades

*Corresponding author for this work

Research output: Contribution to journalJournal articleResearchpeer-review

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Abstract

In this study, the stability and intrinsic dissolution of vacuum compression molded (VCM) amorphous solid dispersions (ASDs) of efavirenz (EFV) were investigated in relation to its solubility limits in seven polymers determined by the melting point depression (MPD) method. The extrapolated solubility limits of EFV at 22 °C ranged from 3 to 68% (w/w) with PVOH being the only polymer suggesting immiscibility with EFV according to both MPD and Hansen solubility parameters (HSPs). All ASDs with EFV loadings below or close to their calculated solubility limit did not show any signs of crystallization upon conditioning for 7 months at either 22 or 37 °C and 23 or 75% relative humidity. However, all ASDs with EFV loading above the solubility limit crystallized at high humidity, while the ASDs with cellulose derived carrier polymers proved kinetically stable at low humidity over 7 months. While the EFV intrinsic dissolution rates from the VCM ASDs were partly depending on the polymer dissolution rate, no correlation was observed between EFV matrix crystallization and its miscibility in the polymer. Altogether, the observations of the study underline the importance of combining preformulation miscibility determination and dissolution studies to rationally decide on both stability and viability of ASD formulations.

Original languageEnglish
Article number122564
JournalInternational Journal of Pharmaceutics
Volume632
Number of pages8
ISSN0378-5173
DOIs
Publication statusPublished - 2023

Keywords

  • Differential scanning calorimetry
  • Flory-Huggins
  • Hansen solubility parameters
  • Polarized light microscopy
  • X-ray diffraction

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