Retention and transit of intestinal mucoadhesive films in rat small intestine.
The retention and transit characteristics of intestinal mucoadhesive film systems have been studied after intraduodenal administration in rats. Small size four layered film preparations, 0.5x0.5 mm, were prepared, where the backing layer (45.1+/-2.9 microm thick) was made of a water-insoluble polymer, ethylcellulose (EC), the surface layer was made of enteric pH-sensitive polymers, Eudragit L100, S100 or HP-55 and the middle layer was made of cellulose membrane. The surface layer was attached to the middle layer with an adhesive layer composed of carboxyvinyl polymer (Hiviswako(R) 103). After administration of ten films to the duodenum, the rats were sacrificed hourly and the distribution of the films in the whole small intestine was directly observed after abdominal incision. The HP-55, Eudragit L100 and S100 film systems were found to adhere to the upper, middle and lower part of the small intestine after 1, 2 and 4 h, respectively, for 2-3 h. Direct inspection study suggests that intestinal mucoadhesive film system has functions of: (1) pH-dependent intestinal adhesion site specificity; (2) adhesion to the intestinal wall; and (3) retention in the small intestinal adhesion site for at least 2 h. Intestinal mucoadhesive film system has been suggested to be a targeting system for drugs to the gastrointestinal tract.
Eaimtrakarn
S
S
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Yamashina-ku, Kyoto, 607-8414, Japan.
Itoh
Y
Y
Kishimoto
J I
JI
Yoshikawa
Y
Y
Shibata
N
N
Takada
K
K
D000268:Adhesiveness; D000818:Animals; D016503:Drug Delivery Systems / Q000379:methods*; D005772:Gastrointestinal Transit; D006863:Hydrogen-Ion Concentration; D007413:Intestinal Mucosa / Q000378:metabolism; D007421:Intestine, Small / Q000378:metabolism*; D008297:Male; D008747:Methylcellulose / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000493:pharmacokinetics*; D011108:Polymers / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics; D011109:Polymethacrylic Acids / Q000008:administration & dosage / Q000493:pharmacokinetics*; D051381:Rats; D017208:Rats, Wistar
D011108:Polymers; D011109:Polymethacrylic Acids; C038300:methylmethacrylate-methacrylic acid copolymer; D008747:Methylcellulose; C053309:hydroxypropyl methylcellulose phthalate