title: Analgesic and anti-inflammatory controlled-released injectable microemulsion: Pseudo-ternary phase diagrams, in vitro, ex vivo and in vivo evaluation.
abstract: OBJECTIVE
  Development of analgesic and anti-inflammatory controlled-released injectable microemulsions utilising lysine clonixinate (LC) as model drug and generally regarded as safe (GRAS) excipients.
  
  
  METHODS
  Different microemulsions were optimised through pseudo-ternary phase diagrams and characterised measuring droplet size, viscosity, ex vivo haemolytic activity and in vitro drug release. The anti-inflammatory and analgesic activity was tested in mice (Hot plate test) and rats (Carrageenan-induced paw edema test) respectively and their activity was compared to an aqueous solution of LC salt.
  
  
  RESULTS
  The aqueous solution showed a faster and shorter response whereas the optimised microemulsion increased significantly (p<0.01) the potency and duration of the analgesic and anti-inflammatory activity after deep intramuscular injection. The droplet size and the viscosity were key factors to control the drug release from the systems and enhance the effect of the formulations.
  
  
  CONCLUSIONS
  The microemulsion consisting of Labrafil®/Lauroglycol®/Polysorbate 80/water with LC (56.25/18.75/15/10, w/w) could be a promising formulation after buccal surgery due to its ability to control the drug release and significantly achieve greater analgesic and anti-inflammatory effect over 24h.
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad Complutense of Madrid, Plaza Ramon y Cajal s/n, Madrid 28040, Spain.
authors.forename: Isabel
authors.initials: I
authors.lastname: Pineros
authors.affiliation: Department of Pharmacology, Faculty of Pharmacy, Universidad Complutense of Madrid, Plaza Ramón y Cajal s/n, Madrid 28040, Spain.
authors.forename: Karla
authors.initials: K
authors.lastname: Slowing
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad Complutense of Madrid, Plaza Ramon y Cajal s/n, Madrid 28040, Spain; Instituto Universitario de Farmacia Industrial (IUFI), School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, Spain. Electronic address: serranod@tcd.ie.
authors.forename: Dolores R
authors.initials: DR
authors.lastname: Serrano
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad Complutense of Madrid, Plaza Ramon y Cajal s/n, Madrid 28040, Spain.
authors.forename: Esther
authors.initials: E
authors.lastname: de Pablo
authors.affiliation: Department of Pharmacy and Pharmaceutical Technology, Faculty of Pharmacy, Universidad Complutense of Madrid, Plaza Ramon y Cajal s/n, Madrid 28040, Spain; Instituto Universitario de Farmacia Industrial (IUFI), School of Pharmacy, University Complutense, Avenida Complutense, 28040 Madrid, Spain.
authors.forename: Maria Paloma
authors.initials: MP
authors.lastname: Ballesteros
mesh_terms: D000700:Analgesics / Q000008:administration & dosage* / Q000737:chemistry; D000818:Animals; D000893:Anti-Inflammatory Agents / Q000008:administration & dosage* / Q000737:chemistry; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003002:Clonixin / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D003692:Delayed-Action Preparations / Q000008:administration & dosage* / Q000737:chemistry; D016503:Drug Delivery Systems / Q000379:methods; D065546:Drug Liberation; D004655:Emulsions / Q000008:administration & dosage* / Q000737:chemistry; D005079:Excipients / Q000737:chemistry; D006801:Humans; D007267:Injections / Q000379:methods; D007273:Injections, Intramuscular / Q000379:methods; D008239:Lysine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry; D008297:Male; D051379:Mice; D010316:Particle Size; D011136:Polysorbates / Q000737:chemistry; D051381:Rats; D017208:Rats, Wistar; D014783:Viscosity
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D003692:Delayed-Action Preparations; D004655:Emulsions; D005079:Excipients; D011136:Polysorbates; C089163:lysine clonixinate; D008239:Lysine; D003002:Clonixin
keywords: Analgesic; Anti-inflammatory; Controlled-release; Depot formulation; Injectable; Lysine clonixinate; Microemulsion; Pseudo-ternary diagrams