Colonoscopic method for estimating the colonic absorption of extended-release dosage forms in dogs

• Published in: European journal of pharmaceutics and biopharmaceutics Vol. 75; no. 2; pp. 238 - 244
• Main Authors: Tajiri, Shinichiro, Kanamaru, Taro, Yoshida, Kazuhiro, Hosoi, Yasue, Fukui, Sachiko, Konno, Tsutomu, Yada, Shuichi, Nakagami, Hiroaki
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.06.2010; Elsevier
• Subjects: Administration, Oral; Animals; Biological and medical sciences; Biological Availability; Bioptome; Colon - metabolism; Colonic absorption; Colonoscopy - methods; Delayed-Action Preparations; Dogs; Endoscope; Extended-release dosage forms; General pharmacology; Humans; Intestinal Absorption; Male; Medical sciences; Pharmaceutical Preparations - administration & dosage; Pharmaceutical Preparations - metabolism; Pharmaceutical technology. Pharmaceutical industry; Pharmacology. Drug treatments; Species Specificity; Extended-release dosage forms; Colonic absorption; Bioptome; Dogs; Endoscope; Fissipedia; Carnivora; Pharmaceutical technology; Controlled release form; Vertebrata; Mammalia; Absorption; Animal; Dosage form; Colon; Pharmacokinetics; Dog
• ISSN: 0939-6411; 1873-3441
• DOI: 10.1016/j.ejpb.2010.03.009

The purpose of this study was to develop a new method using beagle dogs in order to evaluate the colonic absorption properties of oral extended-release (ER) solid dosage forms. The established method is not only noninvasive and inexpensive but full-sized ER dosage forms are also directly administered to the colons of conscious dogs through the anus with an endoscope and modified bioptome. In the method, it was possible to administer the ER dosage forms into the ascending colon of dogs within 30 s–1 min. The colonic absorption of Voltaren-XR (Diclofenac sodium), Glucophage-XR (metformin), Pacif (morphine hydrochloride), Herbesser-R (diltiazem hydrochloride) and Plendil (felodipine), which are currently on the market, were investigated by this method. The relative bioavailabilities of these ER dosage forms to oral drug solution were 100.3%, 42.5%, 60.6%, 46.3% and 29.8%, respectively. Some of these results reflected the human colonic absorption profiles reported in the literature. This newly developed method could provide researchers with an alternative way to predict the human colon absorption performance of oral ER delivery systems.