title: Eutectic, monotectic and immiscibility systems of nimesulide with water-soluble carriers: phase equilibria, solid-state characterisation and in-vivo/pharmacodynamic evaluation.
abstract: OBJECTIVE
  The solid-state interactions of fused mixtures nimesulide (ND) with polyethylene glycol (PEG) 4000, urea or mannitol were studied through constructing thaw-melt phase equilibrium diagrams.
  
  
  METHODS
  The solid-state characteristics were investigated using differential scanning calorimetry (DSC) and X-ray diffraction (XRD). Various types of interactions were identified such as the formation of a eutectic system of ND-PEG 4000, monotectic system of ND-urea and complete solid immiscibility of ND with mannitol. The effects of carrier concentrations on the equilibrium solubility and in-vitro dissolution characteristics were studied.
  
  
  RESULTS
  Linear increases (R(2)  > 0.99) in the aqueous solubility of ND in various concentrations of PEG 4000 and urea were obtained, whereas mannitol did not exhibit any effect on the solubility of ND. Similar trends were obtained with the dissolution efficiency of the fused mixtures of ND with PEG 4000 and urea compared with the corresponding physical mixtures and untreated drug. The analgesic effects of untreated ND and the selected formulations were investigated by evaluating the drug's ability to inhibit the acetic acid-induced writhing response.
  
  
  CONCLUSIONS
  The analgesic effect of ND in a eutectic mixture with PEG 4000 and a monotectic mixture with urea was potentiated by 3.2 and 2.7-fold respectively compared with the untreated drug.
authors.affiliation: Department of Pharmaceutics, Faculty of Pharmacy, Minia University, Minia, Egypt.
authors.forename: Hamdy
authors.initials: H
authors.lastname: Abdelkader
authors.forename: Ossama Y
authors.initials: OY
authors.lastname: Abdallah
authors.forename: Hesham
authors.initials: H
authors.lastname: Salem
authors.forename: Adam W G
authors.initials: AW
authors.lastname: Alani
authors.forename: Raid G
authors.initials: RG
authors.lastname: Alany
mesh_terms: D019342:Acetic Acid; D000818:Animals; D002152:Calorimetry, Differential Scanning; D002626:Chemistry, Pharmaceutical; D016861:Cyclooxygenase Inhibitors / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D004337:Drug Carriers / Q000737:chemistry*; D005079:Excipients / Q000737:chemistry*; D051379:Mice; D010146:Pain / Q000139:chemically induced / Q000188:drug therapy; D011092:Polyethylene Glycols / Q000737:chemistry*; D011205:Povidone / Q000737:chemistry; D012995:Solubility; D013449:Sulfonamides / Q000008:administration & dosage* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D014508:Urea / Q000737:chemistry*; D014867:Water / Q000737:chemistry*; D014961:X-Ray Diffraction
chemical_list: D016861:Cyclooxygenase Inhibitors; D004337:Drug Carriers; D005079:Excipients; D013449:Sulfonamides; D014867:Water; D011092:Polyethylene Glycols; D014508:Urea; D011205:Povidone; D019342:Acetic Acid; C012655:nimesulide
keywords: dissolution rate; eutectic; monotectic; nimesulide; solubility