Development of an oral formulation of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, using n-lauryl-beta-D-maltopyranoside as an absorption enhancer

Citation
I. Sasaki et al., Development of an oral formulation of azetirelin, a new thyrotropin-releasing hormone (TRH) analogue, using n-lauryl-beta-D-maltopyranoside as an absorption enhancer, BIOL PHAR B, 22(6), 1999, pp. 611-615
Citations number
16
Language
INGLESE
art.tipo
Article
Categorie Soggetti
Pharmacology & Toxicology
Journal title
BIOLOGICAL & PHARMACEUTICAL BULLETIN
ISSN journal
0918-6158 → ACNP
Volume
22
Issue
6
Year of publication
1999
Pages
611 - 615
Database
ISI
SICI code
0918-6158(199906)22:6<611:DOAOFO>2.0.ZU;2-I
Abstract
The effects of formulation factors on the enhancement of colonic absorption of azetirelin by n-lauryl-beta-D-maltopyranoside (LM) were studied in rats , Coadministration of LM with a small volume of azetirelin solution to the proximal colon increased the AUC of the drug by 8.7-fold. There were no sig nificant differences in the LM-induced absorption profiles of azetirelin be tween unligated and ligated colon, The addition of a viscous polymer to the drug solution, which delayed the in vitro release of both azetirelin and L M, reduced the promoting effects of LM. These results suggest that the acti on of LM is not affected by sample spreading in the colonic lumen, whereas a rapid release of both azetirelin and LM from the formulation is necessary to maximize the efficacy of LM. Utilizing the balloon sonde method, the ef fects of LM were also confirmed in the colonic loop of dogs. Based on these results, an enteric capsule formulation of azetirelin containing LM and ci tric acid (CA), a potential inhibitor of the bacterial degradation of azeti relin in the distal intestine, was prepared and its performance was evaluat ed in fasted dogs. The bioavailability of azetirelin after the oral adminis tration of this enteric capsule with LM and CA was 43.5% compared with a bi oavailability of 14.9% in capsules without LM and CA. Therefore, the delive ry of azetirelin and LM to the lower intestine, together with a rapid relea se of capsule contents, are feasible for the improved peroral bioavailabili ty of azetirelin.