New sustained-release intraarticular gel formulations based on monolein for local treatment of arthritic diseases

Jonathan Réeff*, Amelie Gaignaux, Jonathan Goole, Carine De Vriese, Karim Amighi

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

26 Citations (Scopus)

Abstract

Inflammatory osteoarthritis (OA) is characterized by painful and destructive inflammatory flares of a single joint, mainly in the back, the knees, the wrists or the hips. Monoarthritis is generally treated by intraarticular (IA) injections of corticosteroids or hyaluronic acid (HA). However, due to their toxicity, the chronic use of corticosteroids should be avoided. The aim of this work was to develop a new slow-release formulation for a parenteral route of administration (e.g., IA). The development's strategy was based on the use of amphiphilic ingredients such as glyceryl monooleate (GMO), which is able to generate viscous crystalline phase structures upon contact with an aqueous fluid (e.g., synovial fluid) to sustain the drug activity over weeks. Clonidine (CLO) was suggested as a small and hydrophilic model drug and HA as a hydrophilic viscoelastic scaffold. Thermal analyses showed that the stability of GMO, HA, and CLO in mixtures with a ratio of 1:1 (wt/wt) was not affected in comparison with the raw materials. In order to obtain a formulation presenting suitable syringeability and containing GMO, CLO, and HA, two elements were found to be essential: a minimum of about 15% (wt/wt) water content and the use of co-solvents such as ethanol (ET) and propylene glycol (PG), approved by the FDA for parenteral use. Several developed gels presented pseudoplastic flow behavior. Moreover, the best composition provided an in vitro release of CLO for about 1 week that was similar to a cubic reference formulation, described by many authors as presenting poor syringeability but the best sustained-release capacity.

Original languageEnglish
Pages (from-to)1731-1741
Number of pages11
JournalDrug Development and Industrial Pharmacy
Volume39
Issue number11
DOIs
Publication statusPublished - Nov 2013
Externally publishedYes

Keywords

  • Arthritic diseases
  • Clonidine
  • Drug delivery
  • Glyceryl monooleate
  • Hyaluronic acid
  • Lipids
  • Liquid crystals
  • Parenteral administration

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