title: Characterization and optimization of GMO-based gels with long term release for intraarticular administration.
abstract: Osteoarthritis is characterized by slow degenerative processes in the articular cartilage within synovial joints. It could be interesting to develop a sustained-release formulation that could be effective on both pain/inflammation and restoration of mechanical integrity of the joint. Recently, an injectable system based on glycerol monooleate (GMO), containing clonidine as a model hydrophilic analgesic/anti-inflammatory drug and hyaluronic acid as a viscoelastic scaffold, showed promising potential as a biodegradable and biocompatible preparation to sustain the drug activity. However, drug release from the system is relatively fast (complete within 1 week) and the underlying drug release mechanisms not fully understood. The aims of this study were: (i) to significantly improve this type of local controlled drug delivery system by further sustaining clonidine release, and (ii) to elucidate the underlying mass transport mechanisms. The addition of FDA-approved inactive ingredients such as sodium oleate or purified soybean oil was found to be highly effective. The release rate could be substantially reduced (e.g., 50% release after 10 days), due to the increased hydrophobicity of the systems, resulting in slower and reduced water uptake and reduced drug mobility. Interestingly, Fick's second law of diffusion could be used to quantitatively describe drug release.
authors: Laboratory of Pharmaceutics and Biopharmaceutics, Université Libre de Bruxelles-ULB, Campus de la Plaine, BC, B-1050 Brussels, Belgium. jreeff@gmail.com
authors: J
authors: J
authors: Réeff
authors: A
authors: A
authors: Gaignaux
authors: J
authors: J
authors: Goole
authors: J
authors: J
authors: Siepmann
authors: F
authors: F
authors: Siepmann
authors: C
authors: C
authors: Jerome
authors: J M
authors: JM
authors: Thomassin
authors: C
authors: C
authors: De Vriese
authors: K
authors: K
authors: Amighi
mesh_terms: D000700:Analgesics / Q000008:administration & dosage / Q000737:chemistry; D003000:Clonidine / Q000008:administration & dosage / Q000737:chemistry*; D003692:Delayed-Action Preparations; D004339:Drug Compounding; D016503:Drug Delivery Systems; D005079:Excipients / Q000737:chemistry; D005782:Gels; D005989:Glycerides / Q000737:chemistry*; D006820:Hyaluronic Acid / Q000008:administration & dosage / Q000737:chemistry*; D057927:Hydrophobic and Hydrophilic Interactions; D007270:Injections, Intra-Articular; D019301:Oleic Acid / Q000737:chemistry; D010003:Osteoarthritis / Q000188:drug therapy; D013024:Soybean Oil / Q000737:chemistry; D013997:Time Factors; D055675:Viscosupplements / Q000008:administration & dosage / Q000737:chemistry
chemical_list: D000700:Analgesics; D003692:Delayed-Action Preparations; D005079:Excipients; D005782:Gels; D005989:Glycerides; D055675:Viscosupplements; D019301:Oleic Acid; C013173:osteum; D013024:Soybean Oil; D006820:Hyaluronic Acid; C005953:monoolein; D003000:Clonidine