Mucoadhesive suppositories of ramosetron hydrochloride utilizing Carbopol.
Suppositories are the preferable dosage form for patients at home or experiencing nausea. Serotonin (5-HT(3))-receptor antagonists are used to treat vomiting in intravenous or oral administration but not suppository form. Ramosetron hydrochloride (RAM) is a new 5-HT(3) antagonist which effectively inhibits vomiting, and we prepared RAM suppositories using Witepsol((R)) H-15 (H-15) containing Carbopol((R)) 934P (CP). The viscosity of suppository base and RAM release properties from suppositories were examined. Plasma RAM concentrations after administration of suppositories to rabbits were estimated and irritation of rectal tissues were observed. Antiemetic effects of suppositories were studied using ferrets. The base viscosity increased with addition of CP. Suppositories containing CP exhibited better absorption in rabbits compared to H-15 suppositories, correlated with release behavior. Suppositories containing 2% CP had 2.5 times larger AUC(0-24 h) than H-15 suppositories, and the MRT was prolonged by 5.8 h compared with i.v. administration. 10% CP suppositories administered to rabbits for 5 days did not irritate the tissues. Antiemetic studies indicated that 2% CP suppository of RAM might have the same effect as i.v. administration. These results suggest that RAM suppositories containing CP are safe and useful in once-a-day dosage form for treatment of chemotherapy-induced nausea.
Yahagi
R
R
Department of Clinical Pharmacy, Hoshi University, Ebara 2-4-41, Shinaga-ku, Tokyo, Japan.
Machida
Y
Y
Onishi
H
H
D000180:Acrylic Resins; D000268:Adhesiveness; D000818:Animals; D019540:Area Under Curve; D001562:Benzimidazoles / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D004337:Drug Carriers; D007413:Intestinal Mucosa / Q000378:metabolism* / Q000473:pathology; D007509:Irritants / Q000633:toxicity; D008297:Male; D011145:Polyvinyls / Q000009:adverse effects / Q000737:chemistry*; D011817:Rabbits; D012007:Rectum / Q000187:drug effects / Q000473:pathology; D012702:Serotonin Antagonists / Q000008:administration & dosage* / Q000009:adverse effects / Q000493:pharmacokinetics; D013488:Suppositories; D014783:Viscosity
D000180:Acrylic Resins; D001562:Benzimidazoles; D004337:Drug Carriers; D007509:Irritants; D011145:Polyvinyls; D012702:Serotonin Antagonists; D013488:Suppositories; C006912:carboxypolymethylene; C071315:ramosetron