Supersaturated lipid-based drug delivery systems–exploring impact of lipid composition type and drug properties on supersaturability and physical stability

Alexandra Roxana Ilie, Brendan T. Griffin*, Ruzica Kolakovic, Maria Vertzoni, Martin Kuentz, René Holm

*Corresponding author for this work

Research output: Contribution to journalJournal articlepeer-review

Abstract

Objective: The objective of this study was to systematically investigate the impact of lipid composition on the ability to design supersaturated lipid-based drug delivery systems (sLBDDS) using three model drugs with different physico-chemical properties. Significance: This study expands the list of investigated sLBDDS by using alternative vehicle compositions relative to current literature. Methods and results: Drug supersaturation was thermally-induced based on previously reported methods and was successfully achieved for celecoxib and cinnarizine. For the novel drug, JNJ-2A, a lower supersaturation potential was observed for the tested LBDDS. For celecoxib and cinnarizine, crystalline precipitate was observed for some sLBDDS upon storage at 25 °C/65%RH, particularly for medium chain sLBDDS (celecoxib) and long chain sLBDDS (cinnarizine). The greater risk of precipitation observed for celecoxib and cinnarizine, particularly at higher apparent degree of supersaturation (aDS) may be related to their higher crystallization tendency as determined by differential scanning calorimetry. Conclusions: The potential for supersaturation in LBDDS, and the risk of precipitation, was found to be highly drug dependent. The apparent degree of supersaturation was considered a major factor impacting the ability to maintain drug supersaturation upon storage.

Original languageEnglish
JournalDrug Development and Industrial Pharmacy
Volume46
Issue number3
Pages (from-to)356-364
Number of pages9
ISSN0363-9045
DOIs
Publication statusPublished - 3 Mar 2020

Keywords

  • formulation development
  • physical stability
  • pre-formulation
  • solubility screening
  • Supersaturated lipid-based drug delivery systems

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