TY - JOUR
T1 - Development of suppository formulation safely improving rectal absorption of rebamipide, a poorly absorbable drug, by utilizing sodium laurate and taurine
AU - Miyake, Masateru
AU - Kamada, Naoki
AU - Oka, Yoshikazu
AU - Mukai, Tadashi
AU - Minami, Takanori
AU - Toguchi, Hajime
AU - Odomi, Masaaki
AU - Ogawara, Ken-ichi
AU - Higaki, Kazutaka
AU - Kimura, Toshikiro
N1 - Copyright:
Copyright 2018 Elsevier B.V., All rights reserved.
PY - 2004/9/14
Y1 - 2004/9/14
N2 - To develop the safe formulation that can safely improve bioavailability of poorly absorbable drugs and that is practically available, we prepared the suppositories of rebamipide, a poorly soluble and poorly absorbable antiulcer drug, by employing the combinatorial use of sodium laurate (C12), an absorption enhancer, with taurine (Tau) or l-glutamine (l-Gln), an adjuvant exerting the cytoprotective action. Although the dissolution of rebamipide from fatty base (FB) suppository prepared using Witepsol H-15 was very slow, it was remarkably improved by the addition of C12 and l-Gln or Tau into the suppository. On the other hand, the dissolution of rebamipide from water-soluble base (WB) suppository prepared using polyethylene glycol was very rapid and the addition of adjuvants did not influence its dissolution so much. Rectal absorption of rebamipide examined in rats was remarkably improved by FB suppository containing C12 or both C12 and Tau, while the enhancing effect of C12 was relatively small in the case of WB suppositories. Biochemical and histopathological studies have confirmed that FB suppository containing both C12 and Tau or l-Gln did not cause any serious local damage, while FB suppository containing C12 only caused the erosion and shrinkage for a lot of rectal epithelial cells. In conclusion, FB suppository employing the combinatorial use of C12 with Tau could be a promising formulation that is effective and safe enough for poorly absorbable drugs to be practically administered.
AB - To develop the safe formulation that can safely improve bioavailability of poorly absorbable drugs and that is practically available, we prepared the suppositories of rebamipide, a poorly soluble and poorly absorbable antiulcer drug, by employing the combinatorial use of sodium laurate (C12), an absorption enhancer, with taurine (Tau) or l-glutamine (l-Gln), an adjuvant exerting the cytoprotective action. Although the dissolution of rebamipide from fatty base (FB) suppository prepared using Witepsol H-15 was very slow, it was remarkably improved by the addition of C12 and l-Gln or Tau into the suppository. On the other hand, the dissolution of rebamipide from water-soluble base (WB) suppository prepared using polyethylene glycol was very rapid and the addition of adjuvants did not influence its dissolution so much. Rectal absorption of rebamipide examined in rats was remarkably improved by FB suppository containing C12 or both C12 and Tau, while the enhancing effect of C12 was relatively small in the case of WB suppositories. Biochemical and histopathological studies have confirmed that FB suppository containing both C12 and Tau or l-Gln did not cause any serious local damage, while FB suppository containing C12 only caused the erosion and shrinkage for a lot of rectal epithelial cells. In conclusion, FB suppository employing the combinatorial use of C12 with Tau could be a promising formulation that is effective and safe enough for poorly absorbable drugs to be practically administered.
KW - Absorption enhancer
KW - Cytoprotection
KW - Histopathology
KW - Suppository
KW - Taurine
KW - l-Glutamine
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U2 - 10.1016/j.jconrel.2004.06.007
DO - 10.1016/j.jconrel.2004.06.007
M3 - Article
C2 - 15342181
AN - SCOPUS:4444267520
VL - 99
SP - 63
EP - 71
JO - Journal of Controlled Release
JF - Journal of Controlled Release
SN - 0168-3659
IS - 1
ER -