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Eur J Pharm Sci. 2016 Aug 25;91:11-9. doi: 10.1016/j.ejps.2016.05.013. Epub 2016 May 13.

Effectiveness of supersaturation promoting excipients on albendazole concentrations in upper gastrointestinal lumen of fasted healthy adults.

Author information

1
Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece.
2
Department of Gastroenterology, Red Cross Hospital of Athens, Greece.
3
Product Development, GlaxoSmithKline, Ware, UK.
4
Faculty of Pharmacy, School of Health Sciences, National and Kapodistrian University of Athens, Zografou, Greece. Electronic address: reppas@pharm.uoa.gr.

Abstract

PURPOSE:

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.

MATERIALS AND 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.

KEYWORDS:

Albendazole; HPMC; Humans; Lipid excipients; Luminal concentrations; Supersaturation

PMID:
27185297
DOI:
10.1016/j.ejps.2016.05.013
[Indexed for MEDLINE]

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