New sustained-release intraarticular gel formulations based on monolein for local treatment of arthritic diseases.
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.
Laboratory of Pharmaceutics and Biopharmaceutics, Pharmacy Institute, Université Libre de Bruxelles (ULB) , Campus Plaine, Brussels , Belgium.
Jonathan
J
Réeff
Amelie
A
Gaignaux
Jonathan
J
Goole
Carine
C
De Vriese
Karim
K
Amighi
D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D001168:Arthritis / Q000188:drug therapy* / Q000276:immunology; D055598:Chemical Phenomena; D003000:Clonidine / Q000008:administration & dosage / Q000737:chemistry* / Q000627:therapeutic use; D003692:Delayed-Action Preparations / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D004338:Drug Combinations; D004339:Drug Compounding; D004355:Drug Stability; D000431:Ethanol / Q000737:chemistry; D005079:Excipients / Q000737:chemistry*; D005782:Gels; D005989:Glycerides / Q000737:chemistry*; D006801:Humans; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000627:therapeutic use; D007270:Injections, Intra-Articular; D055595:Mechanical Phenomena; D008958:Models, Molecular; D019946:Propylene Glycol / Q000737:chemistry; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D014783:Viscosity
D000700:Analgesics; D000894:Anti-Inflammatory Agents, Non-Steroidal; D003692:Delayed-Action Preparations; D004338:Drug Combinations; D005079:Excipients; D005782:Gels; D005989:Glycerides; D012997:Solvents; D000431:Ethanol; D019946:Propylene Glycol; D006820:Hyaluronic Acid; C005953:monoolein; D003000:Clonidine