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J Pharm Sci. 2016 Sep;105(9):2896-2903. doi: 10.1016/j.xphs.2016.04.037. Epub 2016 Jun 30.

Evaluation of the Impact of Excipients and an Albendazole Salt on Albendazole Concentrations in Upper Small Intestine Using an In Vitro Biorelevant Gastrointestinal Transfer (BioGIT) System.

Author information

1
Faculty of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece.
2
Strathclyde Institute for Pharmacy and Biomedical Sciences, University of Strathclyde, Scotland, UK.
3
Product Development, GlaxoSmithKline, Stevenage, UK.
4
Product Development, GlaxoSmithKline, Ware, UK.
5
Faculty of Pharmacy, National and Kapodistrian University of Athens, Zografou, Greece. Electronic address: reppas@pharm.uoa.gr.

Abstract

An in vitro biorelevant gastrointestinal transfer (BioGIT) system was assessed for its ability to mimic recently reported albendazole concentrations in human upper small intestine after administration of free base suspensions to fasted adults in absence and in presence of supersaturation promoting excipients (hydroxypropylmethylcellulose and lipid self-emulsifying vehicles). The in vitro method was also used to evaluate the likely impact of using the sulfate salt on albendazole concentrations in upper small intestine. In addition, BioGIT data were compared with equilibrium solubility data of the salt and the free base in human aspirates and biorelevant media. The BioGIT system adequately simulated the average albendazole gastrointestinal transfer process and concentrations in upper small intestine after administration of the free base suspensions to fasted adults. However, the degree of supersaturation observed in the duodenal compartment was greater than in vivo. Albendazole sulfate resulted in minimal increase of albendazole concentrations in the duodenal compartment of the BioGIT, despite improved equilibrium solubility observed in human aspirates and biorelevant media, indicating that the use of a salt is unlikely to lead to any significant oral absorption advantage for albendazole.

KEYWORDS:

BioGIT; HPMC E5; albendazole salts; dissolution; gastrointestinal transfer; lipid excipients; poorly soluble weak base; precipitation inhibitor; supersaturation

PMID:
27372549
DOI:
10.1016/j.xphs.2016.04.037
[Indexed for MEDLINE]

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