Optimization of suppository preparation containing sodium laurate and taurine that can safely improve rectal absorption of rebamipide.
We previously reported that the fatty base suppository containing sodium laurate (C12) and taurine (Tau) (C12-Tau suppository) could enhance the colonic absorption of rebamipide, a poorly water-soluble and poorly absorbable drug, without any serious mucosal damages in rats. In the preset study, in order to make C12-Tau suppositories available for practical use, the scaling-up studies of animal and formulation size were performed, compared with the suppositories containing sodium caprate (C10) (C10 suppository) at the same amounts as those contained in the commercial products. Twenty-mg C12 improved the dissolution of rebamipide from suppository remarkably and the addition of 30-mg Tau only slightly decreased the dissolution rate. The absorption of rebamipide from rabbit rectum was more markedly improved by suppositories containing C12 than C10 suppositories. Although Tau tended to attenuate the absorption-enhancing effect of C12, several C12-Tau suppositories kept high bioavailability values, which were much higher than control. Histopathological studies showed that Tau exerted the cytoprotective action and that C12-Tau suppositories were better than C10 suppositories in safety. Considering the balance between efficacy and safety, the suppository containing 10- or 20-mg C12 with 30-mg Tau is better than C10 suppositories as commercial products and could be promising for practical use in human.
Miyake
Masateru
M
Formulation Development 1, Formulation Research Institute, Otsuka Pharmaceutical Co. Ltd., 224-18 Ebino, Hiraishi, Kawauchi-cho, Tokushima 771-0182, Japan.
Minami
Takanori
T
Oka
Yoshikazu
Y
Kamada
Naoki
N
Yamazaki
Hiroyuki
H
Kato
Yusuke
Y
Mukai
Tadashi
T
Toguchi
Hajime
H
Odomi
Masaaki
M
Ogawara
Ken-ichi
K
Higaki
Kazutaka
K
Kimura
Toshikiro
T
D000285:Administration, Rectal; D000409:Alanine / Q000008:administration & dosage / Q000009:adverse effects / Q000031:analogs & derivatives* / Q000737:chemistry / Q000493:pharmacokinetics; D000818:Animals; D001682:Biological Availability; D004337:Drug Carriers / Q000737:chemistry*; D004339:Drug Compounding; D007275:Injections, Intravenous; D007408:Intestinal Absorption; D007850:Lauric Acids / Q000737:chemistry*; D008297:Male; D015363:Quinolones / Q000008:administration & dosage / Q000009:adverse effects / Q000737:chemistry / Q000493:pharmacokinetics*; D011817:Rabbits; D012007:Rectum / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D012995:Solubility; D013488:Suppositories; D013654:Taurine / Q000737:chemistry*
D004337:Drug Carriers; D007850:Lauric Acids; D015363:Quinolones; D013488:Suppositories; C030358:lauric acid; D013654:Taurine; C052785:rebamipide; D000409:Alanine