Abstract
In order to develop a novel oral formulation that can safely improve the intestinal absorption of poorly absorbable drugs, polyamines such as spermine (SPM) and spermidine (SPD) was examined as an absorption enhancing adjuvant in rats. The absorption of rebamipide, classified into BCS Class IV, from colon was significantly improved by SPM or SPD, and the enhancing ability of SPM was larger than that of SPD. As a possible mixing and/or interaction of polyamines with bile acids were expected, the combinatorial use of sodium taurocholate (STC) with polyamines was also examined. The absorption of rebamipide was drastically improved by the combinatorial use of SPM or SPD with STC. As STC itself did not enhance the absorption of rebamipide so much, it was considered that polyamines and STC had a synergistic enhancing effect. In-vivo oral absorption study was also performed to investigate the effectiveness and safety of polyamines and their combinatorial use with STC in rats. Although the enhancing effect slightly attenuated comparing with the in-situ loop study, the absorption of rebamipide was significantly improved and the combinatorial use of 10 mM SPM with 25 mM STC showed the largest enhancing effect. Histopathological studies clearly showed that any significant change in stomach and duodenum was not caused by SPM (10 mM), SPD (10 mM) or their combinatorial use with STC (25 mM) at 1.5 or 8.0 h after oral administration. Taken all together, polyamines, especially SPM, and its combinatorial use with STC could improve the absorption of poorly absorbable drugs without any significant changes in gastrointestinal tract after oral administration in rats.
| Original language | English |
|---|---|
| Pages (from-to) | 27-34 |
| Number of pages | 8 |
| Journal | Journal of Controlled Release |
| Volume | 111 |
| Issue number | 1-2 |
| DOIs | |
| Publication status | Published - Mar 10 2006 |
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Keywords
- Bile acids
- Gastrointestinal absorption
- Histopathology
- Membrane permeability
- Polyamines
ASJC Scopus subject areas
- Pharmaceutical Science
Cite this
Novel oral formulation safely improving intestinal absorption of poorly absorbable drugs : Utilization of polyamines and bile acids. / Miyake, Masateru; Minami, Takanori; Hirota, Masao; Toguchi, Hajime; Odomi, Masaaki; Ogawara, Ken Ichi; Higaki, Kazutaka; Kimura, Toshikiro.
In: Journal of Controlled Release, Vol. 111, No. 1-2, 10.03.2006, p. 27-34.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Novel oral formulation safely improving intestinal absorption of poorly absorbable drugs
T2 - Utilization of polyamines and bile acids
AU - Miyake, Masateru
AU - Minami, Takanori
AU - Hirota, Masao
AU - Toguchi, Hajime
AU - Odomi, Masaaki
AU - Ogawara, Ken Ichi
AU - Higaki, Kazutaka
AU - Kimura, Toshikiro
PY - 2006/3/10
Y1 - 2006/3/10
N2 - In order to develop a novel oral formulation that can safely improve the intestinal absorption of poorly absorbable drugs, polyamines such as spermine (SPM) and spermidine (SPD) was examined as an absorption enhancing adjuvant in rats. The absorption of rebamipide, classified into BCS Class IV, from colon was significantly improved by SPM or SPD, and the enhancing ability of SPM was larger than that of SPD. As a possible mixing and/or interaction of polyamines with bile acids were expected, the combinatorial use of sodium taurocholate (STC) with polyamines was also examined. The absorption of rebamipide was drastically improved by the combinatorial use of SPM or SPD with STC. As STC itself did not enhance the absorption of rebamipide so much, it was considered that polyamines and STC had a synergistic enhancing effect. In-vivo oral absorption study was also performed to investigate the effectiveness and safety of polyamines and their combinatorial use with STC in rats. Although the enhancing effect slightly attenuated comparing with the in-situ loop study, the absorption of rebamipide was significantly improved and the combinatorial use of 10 mM SPM with 25 mM STC showed the largest enhancing effect. Histopathological studies clearly showed that any significant change in stomach and duodenum was not caused by SPM (10 mM), SPD (10 mM) or their combinatorial use with STC (25 mM) at 1.5 or 8.0 h after oral administration. Taken all together, polyamines, especially SPM, and its combinatorial use with STC could improve the absorption of poorly absorbable drugs without any significant changes in gastrointestinal tract after oral administration in rats.
AB - In order to develop a novel oral formulation that can safely improve the intestinal absorption of poorly absorbable drugs, polyamines such as spermine (SPM) and spermidine (SPD) was examined as an absorption enhancing adjuvant in rats. The absorption of rebamipide, classified into BCS Class IV, from colon was significantly improved by SPM or SPD, and the enhancing ability of SPM was larger than that of SPD. As a possible mixing and/or interaction of polyamines with bile acids were expected, the combinatorial use of sodium taurocholate (STC) with polyamines was also examined. The absorption of rebamipide was drastically improved by the combinatorial use of SPM or SPD with STC. As STC itself did not enhance the absorption of rebamipide so much, it was considered that polyamines and STC had a synergistic enhancing effect. In-vivo oral absorption study was also performed to investigate the effectiveness and safety of polyamines and their combinatorial use with STC in rats. Although the enhancing effect slightly attenuated comparing with the in-situ loop study, the absorption of rebamipide was significantly improved and the combinatorial use of 10 mM SPM with 25 mM STC showed the largest enhancing effect. Histopathological studies clearly showed that any significant change in stomach and duodenum was not caused by SPM (10 mM), SPD (10 mM) or their combinatorial use with STC (25 mM) at 1.5 or 8.0 h after oral administration. Taken all together, polyamines, especially SPM, and its combinatorial use with STC could improve the absorption of poorly absorbable drugs without any significant changes in gastrointestinal tract after oral administration in rats.
KW - Bile acids
KW - Gastrointestinal absorption
KW - Histopathology
KW - Membrane permeability
KW - Polyamines
UR - http://www.scopus.com/inward/record.url?scp=33344468568&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=33344468568&partnerID=8YFLogxK
U2 - 10.1016/j.jconrel.2005.11.010
DO - 10.1016/j.jconrel.2005.11.010
M3 - Article
C2 - 16410031
AN - SCOPUS:33344468568
VL - 111
SP - 27
EP - 34
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1-2
ER -