title: The influence of non-ionisable excipients on precipitation parameters measured using the CheqSol method.
abstract: OBJECTIVE
  The aim of this study was to determine the influence of non-ionisable excipients hydroxypropyl-β-cyclodextrin (HPβCD) and poloxamers 407 and 188 on the supersaturation and precipitation kinetics of ibuprofen, gliclazide, propranolol and atenolol induced through solution pH shifts using the CheqSol method.
  
  
  METHODS
  The drug's kinetic and intrinsic aqueous solubilities were measured in the presence of increasing excipient concentrations using the CheqSol method. Experimental data rate of change of pH with time was also examined to determine excipient-induced parachute effects and influence on precipitation rates.
  
  
  RESULTS
  The measured kinetic and intrinsic solubilities provide a determination of the influence of each excipient on supersaturation index, and the area under the CheqSol curve can measure the parachute capability of excipients. The excipients influence on precipitation kinetics can be measured with novel parameters; for example, the precipitation pH or percentage ionised drug at the precipitation point, which provide further information on the excipient-induced changes in precipitation performance.
  
  
  CONCLUSIONS
  This method can therefore be employed to measure the influence of non-ionisable excipients on the kinetic solubility behaviour of supersaturated solutions of ionisable drugs and to provide data, which discriminates between excipient systems during precipitation.
authors.affiliation: Cancer Research UK Formulation Unit, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Kelly
authors.initials: K
authors.lastname: Etherson
authors.affiliation: Cancer Research UK Formulation Unit, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Gavin
authors.initials: G
authors.lastname: Halbert
authors.affiliation: Cancer Research UK Formulation Unit, Strathclyde Institute of Pharmacy and Biomedical Sciences, University of Strathclyde, Glasgow, UK.
authors.forename: Moira
authors.initials: M
authors.lastname: Elliott
mesh_terms: D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001262:Atenolol / Q000737:chemistry*; D002626:Chemistry, Pharmaceutical; D005079:Excipients / Q000737:chemistry*; D005907:Gliclazide / Q000737:chemistry*; D006863:Hydrogen-Ion Concentration; D007052:Ibuprofen / Q000737:chemistry*; D007700:Kinetics; D019999:Pharmaceutical Solutions; D020442:Poloxamer / Q000737:chemistry*; D011433:Propranolol / Q000737:chemistry*; D012995:Solubility; D012996:Solutions; D047392:beta-Cyclodextrins / Q000737:chemistry*
chemical_list: D005079:Excipients; D019999:Pharmaceutical Solutions; D012996:Solutions; D047392:beta-Cyclodextrins; D020442:Poloxamer; D000073738:2-Hydroxypropyl-beta-cyclodextrin; D001262:Atenolol; D011433:Propranolol; D005907:Gliclazide; D007052:Ibuprofen
keywords: biopharmaceutics and drug disposition; dosage form design and characterisation; drug characterisation studies; pharmaceutical analysis; pharmaceutics and drug delivery