Development of suppository formulation safely improving rectal absorption of rebamipide, a poorly absorbable drug, by utilizing sodium laurate and taurine.
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.
Miyake
Masateru
M
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Okayama University, 1-1-1 Tsushima-naka Okayama, Japan.
Kamada
Naoki
N
Oka
Yoshikazu
Y
Mukai
Tadashi
T
Minami
Takanori
T
Toguchi
Hajime
H
Odomi
Masaaki
M
Ogawara
Ken-ichi
K
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000409:Alanine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000493:pharmacokinetics* / Q000633:toxicity; D000818:Animals; D019540:Area Under Curve; D001682:Biological Availability; D002626:Chemistry, Pharmaceutical; D007408:Intestinal Absorption; D007413:Intestinal Mucosa / Q000187:drug effects / Q000473:pathology; D007850:Lauric Acids / Q000737:chemistry*; D008297:Male; D015363:Quinolones / Q000008:administration & dosage / Q000493:pharmacokinetics* / Q000633:toxicity; D051381:Rats; D011919:Rats, Inbred Strains; D012995:Solubility; D013488:Suppositories / Q000737:chemistry* / Q000493:pharmacokinetics; D013654:Taurine / Q000737:chemistry*; D014280:Triglycerides / Q000737:chemistry
D007850:Lauric Acids; D015363:Quinolones; D013488:Suppositories; D014280:Triglycerides; C030358:lauric acid; C009683:witepsol; D013654:Taurine; C052785:rebamipide; D000409:Alanine