title: In-vitro evaluation of performance of solid immediate release dosage forms of weak bases in upper gastrointestinal lumen: experience with miconazole and clopidogrel salts.
abstract: OBJECTIVE
  Evaluate the impact of salt and counterion identity on performance of solid immediate release dosage forms of miconazole and clopidogrel, respectively, in fasted upper gastrointestinal lumen using in-vitro methodologies.
  
  
  METHODS
  Two miconazole chemical forms (free base and nitrate salt) and three clopidogrel chemical forms (bisulfate, besylate and hydrochloride salts) were studied. Solubilities of miconazole forms were measured in simulated gastric fluids. Gastrointestinal transfer of the five chemical forms was evaluated by using a flow-through, three-compartmental set-up. Precipitation in duodenal compartment was evaluated by using solutions in gastric compartment.
  
  
  RESULTS
  Solubilities in simulated gastric fluids, concentrations in duodenal compartment and solubilities in duodenal compartment indicated poorer performance of miconazole nitrate vs. miconazole free base in upper gastrointestinal lumen. In line with the low crystallization tendency of free base, duodenal precipitation of miconazole from a free base solution was limited. Concentrations in duodenal compartment indicated that counterion identity does not affect the performance of clopidogrel; precipitation in duodenal compartment was extensive in all cases.
  
  
  CONCLUSIONS
  Miconazole data indicate that salts may adversely affect performance of immediate release dosage forms of weak bases. In line with existing in-vivo data, clopidogrel data indicate that counterion identity is unimportant for the performance of clopidogrel salts in upper intestinal lumen.
authors.affiliation: Faculty of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Dimopoulou
authors.affiliation: Faculty of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Canella-Stefania
authors.initials: CS
authors.lastname: Mourouti
authors.affiliation: Faculty of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Vertzoni
authors.affiliation: Faculty of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Mira
authors.initials: M
authors.lastname: Symillides
authors.affiliation: Faculty of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
mesh_terms: D000284:Administration, Oral; D002214:Capsules; D002712:Chlorides / Q000737:chemistry*; D000077144:Clopidogrel; D004337:Drug Carriers; D004339:Drug Compounding; D004386:Duodenum / Q000737:chemistry*; D005215:Fasting; D005750:Gastric Juice / Q000737:chemistry; D005780:Gelatin / Q000737:chemistry; D006244:Hardness; D006863:Hydrogen-Ion Concentration; D007419:Intestinal Secretions / Q000737:chemistry; D008825:Miconazole / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry*; D008956:Models, Chemical; D009566:Nitrates / Q000008:administration & dosage / Q000737:chemistry*; D012995:Solubility; D013270:Stomach / Q000737:chemistry*; D013431:Sulfates / Q000008:administration & dosage / Q000737:chemistry*; D013988:Ticlopidine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000737:chemistry; D013997:Time Factors
chemical_list: D002214:Capsules; D002712:Chlorides; D004337:Drug Carriers; D009566:Nitrates; D013431:Sulfates; D008825:Miconazole; D005780:Gelatin; D000077144:Clopidogrel; D013988:Ticlopidine
keywords: clopidogrel; miconazole; precipitation; salts; supersaturation