Design and evaluation of ondansetron liquid suppository for the treatment of emesis

• Published in: Archives of pharmacal research 2013, 36(5), , pp.586-592
• Main Authors: Ban, Eunmi, Kim, Chong-Kook
• Format: Article
• Language: English
• Subjects: Adhesiveness; Administration, Oral; Administration, Rectal; Animals; Antiemetics - administration & dosage; Antiemetics - adverse effects; Antiemetics - pharmacokinetics; Antiemetics - therapeutic use; Biological Availability; Dose-Response Relationship, Drug; Drug Carriers - chemistry; Drug Design; Half-Life; Intestinal Mucosa - drug effects; Intestinal Mucosa - metabolism; Male; Medicine; Ondansetron - administration & dosage; Ondansetron - adverse effects; Ondansetron - pharmacokinetics; Ondansetron - therapeutic use; Pharmacology/Toxicology; Pharmacy; Phase Transition; Poloxamer - chemistry; Rats; Rats, Sprague-Dawley; Research Article; Rheology; Solutions; Suppositories; Temperature; Viscosity; Vomiting - drug therapy; 약학
• ISSN: 0253-6269; 1976-3786
• DOI: 10.1007/s12272-013-0049-y

The thermosensitive–mucoadhesive ondansetron liquid suppository (tmOLS) was developed to enhance patient compliance and bioavailability in high-risk patients receiving highly emetogenic therapy and having difficulty in swallowing, The thermosensitive–mucoadhesive liquid suppository bases were formulated using poloxamers (P407 and P188) and hydroxypropylmethyl cellulose (HPMC). The physicochemical properties of the liquid suppository bases were characterized by their gelation temperature, mucoadhesive force, rheological properties, and in vitro release. Rectal mucosal damage following rectal administration of tmOLS in rats was assessed using microscopy. Pharmacokinetic analyses were performed to compare tmOLS administered via the rectal route to ondansetron solution administered orally. The liquid suppository base of tmOLS contained P407, P188, and HPMC in the ratio 18:20:0.8, was in the liquid state at room temperature, underwent gelation at body temperature. Area under the curve and half-life (t 1/2 ) of ondansetron were significantly higher in the tmOLS-treated group, indicating that the formulation bypassed the first-pass metabolism and that it was released slowly from the tmOLS because of the formation of mucoadhesive gel state. Furthermore, the t 1/2 of tmOLS was two-fold that of the oral solution. Thus, tmOLS could be administered to patients who have difficulty in swallowing; however, adjustments in dosing interval may be needed.