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Novel oral formulation safely improving intestinal absorption of poorly absorbable drugs: utilization of polyamines and bile acids.
- Source :
-
Journal of controlled release : official journal of the Controlled Release Society [J Control Release] 2006 Mar 10; Vol. 111 (1-2), pp. 27-34. Date of Electronic Publication: 2006 Jan 10. - Publication Year :
- 2006
-
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.
- Subjects :
- Adjuvants, Pharmaceutic administration & dosage
Administration, Oral
Alanine administration & dosage
Alanine blood
Alanine pharmacokinetics
Animals
Anti-Ulcer Agents administration & dosage
Anti-Ulcer Agents pharmacokinetics
Area Under Curve
Biological Availability
Colon drug effects
Colon metabolism
Gastric Mucosa drug effects
Gastric Mucosa metabolism
Male
Quinolones administration & dosage
Quinolones blood
Rats
Rats, Sprague-Dawley
Spermidine administration & dosage
Spermidine pharmacology
Spermine administration & dosage
Spermine pharmacology
Taurocholic Acid administration & dosage
Taurocholic Acid pharmacology
Adjuvants, Pharmaceutic pharmacology
Alanine analogs & derivatives
Intestinal Absorption drug effects
Quinolones pharmacokinetics
Subjects
Details
- Language :
- English
- ISSN :
- 0168-3659
- Volume :
- 111
- Issue :
- 1-2
- Database :
- MEDLINE
- Journal :
- Journal of controlled release : official journal of the Controlled Release Society
- Publication Type :
- Academic Journal
- Accession number :
- 16410031
- Full Text :
- https://doi.org/10.1016/j.jconrel.2005.11.010