Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions

Ka̅rlis Bērziņš, Sara J. Fraser-Miller, Greg F. Walker, Thomas Rades, Keith C. Gordon

Research output: Contribution to journalArticlepeer-review

11 Citations (Scopus)

Abstract

Compression-induced destabilization was investigated in various celecoxib amorphous solid dispersions containing hydroxypropyl methylcellulose (HPMC), poly(vinylpyrrolidone)/vinyl acetate copolymer (PVP/VA), or poly(vinylpyrrolidone) (PVP) at a concentration range of 1-10% w/w. Pharmaceutically relevant (125 MPa pressure with a minimal dwell time) and extreme (500 MPa pressure with a 60 s dwell time) compression conditions were applied to these systems, and the changes in their physical stability were monitored retrospectively (i.e., in the supercooled state) using dynamic differential scanning calorimetry (DSC) and low-frequency Raman (LFR) measurements over a broad temperature range (-90 to 200 and -150 to 140 °C, respectively). Both techniques revealed similar changes in the crystallization behavior between samples, where the application of a higher compression force of 500 MPa resulted in a more pronounced destabilization effect that was progressively mitigated with increasing polymer content. However, other aspects such as more favorable intermolecular interactions did not appear to have any effect on reducing this undesirable effect. Additionally, for the first time, LFR spectroscopy was used as a viable technique to determine the secondary or local glass-transition temperature, Tg,β, a major indicator of the physical stability of neat amorphous pharmaceutical systems.
Original languageEnglish
Pages (from-to)3882-3893
Number of pages12
JournalMolecular Pharmaceutics
Volume18
Issue number10
DOIs
Publication statusPublished - 4 Oct 2021
Externally publishedYes

Keywords

  • amorphous drugs
  • celecoxib
  • compression-induced destabilization
  • differential scanning calorimetry
  • hydroxypropyl methylcellulose
  • low-frequency Raman spectroscopy
  • poly(vinylpyrrolidone)
  • poly(vinylpyrrolidone)/vinyl acetate copolymer

Fingerprint

Dive into the research topics of 'Investigation on Formulation Strategies to Mitigate Compression-Induced Destabilization in Supersaturated Celecoxib Amorphous Solid Dispersions'. Together they form a unique fingerprint.

Cite this