Τίτλος:
Effectiveness of supersaturation promoting excipients on albendazole concentrations in upper gastrointestinal lumen of fasted healthy adults
Γλώσσες Τεκμηρίου:
Αγγλικά
Περίληψη:
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 40 min 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. © 2015 Elsevier B.V.
Συγγραφείς:
Kourentas, A.
Vertzoni, M.
Symillides, M.
Goumas, K.
Gibbon, R.
Butler, J.
Reppas, C.
Περιοδικό:
EUROPEAN JOURNAL OF PHARMACEUTICAL SCIENCES
Λέξεις-κλειδιά:
albendazole; cremophor; excipient; glass; hydroxypropylmethylcellulose; miglyol; polysorbate 80; albendazole; excipient; hydroxypropylmethylcellulose; lipid, adult; Article; diet restriction; duodenum; human; human experiment; lipophilicity; male; normal human; particle size; precipitation; priority journal; stomach; stomach content; stomach emptying; stomach juice; stomach secretion; supersaturation; thermodynamics; chemistry; clinical trial; metabolism; small intestine; stomach mucosa; suspension; young adult, Adult; Albendazole; Excipients; Gastric Emptying; Gastric Mucosa; Humans; Hypromellose Derivatives; Intestine, Small; Lipids; Male; Suspensions; Young Adult
DOI:
10.1016/j.ejps.2016.05.013
