title: Effectiveness of supersaturation promoting excipients on albendazole concentrations in upper gastrointestinal lumen of fasted healthy adults.
abstract: OBJECTIVE
  To evaluate the impact of dosage form relevant levels of a polymeric precipitation inhibitor and of lipid excipients on supersaturation of upper gastrointestinal contents with albendazole, a lipophilic weak base.
  
  
  METHODS
  Albendazole concentrations in stomach and in duodenum were evaluated after administration of 1) a suspension in water (Susp-Control), 2) a suspension in water in which hydroxyprolylmethylcellulose E5 (HPMC E5) had been pre-dissolved (Susp-HPMC), and 3) and 4) two contrasting designs of lipid based suspensions dispersed in water (Susp-IIIA and Susp-IV), on a cross-over basis to fasted healthy adults.
  
  
  RESULTS
  Limited, but statistically significant supersaturation of duodenal contents was observed after Susp-HPMC, Susp-IIIA, and Susp-IV; supersaturation was more consistent after Susp-HPMC administration. Based on total albendazole amount per volume, gastric secretions did not significantly alter volumes of bulk gastric contents during the first 40min post administration of a glass of non-caloric water-based fluid. Αlbendazole gastric concentrations were higher than in the administered suspensions, but similar for all four formulations. Gastric emptying of albendazole after administration of Susp-Control or Susp-HPMC was slower than after administration of Susp-IIIA or Susp-IV.
  
  
  CONCLUSIONS
  Small amounts of HPMC E5 were as effective as lipid excipients in achieving supersaturation of duodenal contents with albendazole, a fast precipitating weak base, in fasted adults. However, compared with the effect of HPMC E5 the effect of lipid excipients was delayed and variable.
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Alexandros
authors.initials: A
authors.lastname: Kourentas
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Vertzoni
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece.
authors.forename: Mira
authors.initials: M
authors.lastname: Symillides
authors.affiliation: Department of Gastroenterology, Red Cross Hospital of Athens, Greece.
authors.forename: Konstantinos
authors.initials: K
authors.lastname: Goumas
authors.affiliation: Product Development, GlaxoSmithKline, Ware, UK.
authors.forename: Robert
authors.initials: R
authors.lastname: Gibbon
authors.affiliation: Product Development, GlaxoSmithKline, Ware, UK.
authors.forename: James
authors.initials: J
authors.lastname: Butler
authors.affiliation: Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece. Electronic address: reppas@pharm.uoa.gr.
authors.forename: Christos
authors.initials: C
authors.lastname: Reppas
mesh_terms: D000328:Adult; D015766:Albendazole / Q000737:chemistry* / Q000493:pharmacokinetics*; D005079:Excipients / Q000737:chemistry* / Q000493:pharmacokinetics*; D005746:Gastric Emptying; D005753:Gastric Mucosa / Q000378:metabolism*; D006801:Humans; D065347:Hypromellose Derivatives / Q000737:chemistry / Q000493:pharmacokinetics; D007421:Intestine, Small / Q000378:metabolism*; D008055:Lipids / Q000737:chemistry / Q000493:pharmacokinetics; D008297:Male; D013535:Suspensions; D055815:Young Adult
chemical_list: D005079:Excipients; D008055:Lipids; D013535:Suspensions; D065347:Hypromellose Derivatives; D015766:Albendazole
keywords: Albendazole; HPMC; Humans; Lipid excipients; Luminal concentrations; Supersaturation