Application of pressure-controlled colon delivery capsule to oral administration of glycyrrhizin in dogs.
A colon delivery system has been used to improve the bioavailability of glycyrrhizin, a glycoside of glycyrrhetic acid. The bioavailability of glycyrrhizin is low when administered in conventional oral galenic dosage forms because glycyrrhizin is enzymatically hydrolysed both in the stomach and in the intestine. It was reasoned that if large amounts of glycyrrhizin were directly delivered to the colon, enzymatic activity should be reduced due to saturation so that intact glycyrrhizin could be absorbed into the systemic circulation. Based on this assumption, pressure-controlled colon delivery capsules (PCDCs) were used as a colon delivery system. Eight types of glycyrrhizin solution were prepared and were introduced into PCDCs. After oral administration of the test PCDCs to beagle dogs, blood samples were obtained over 24 h and plasma glycyrrhizin concentrations were measured by an HPLC method. With PCDCs containing aqueous glycyrrhizin and propylene glycol solutions, plasma glycyrrhizin levels were extremely low and the bioavailabilities of glycyrrhizin were 0.6% and 0.4%, respectively. When Labrasol was added to both types of glycyrrhizin solution, the bioavailability was improved to 4.6% for aqueous solution and 3.8% for propylene glycol solution. When a surfactant, Polysorbate 80, was added in combination with Labrasol, synergistic effects were not obtained. Furthermore, dose-dependent effects of Polysorbate 80 were not obtained. Labrasol, which is a component of self-emulsifying drug delivery systems (SEDDS), has been shown to strongly improve the bioavailability of glycyrrhizin from the colon.
Shibata
N
N
Department of Pharmacokinetics, Kyoto Pharmaceutical University, Japan.
Ohno
T
T
Shimokawa
T
T
Hu
Z
Z
Yoshikawa
Y
Y
Koga
K
K
Murakami
M
M
Takada
K
K
D000284:Administration, Oral; D000818:Animals; D000890:Anti-Infective Agents / Q000008:administration & dosage / Q000493:pharmacokinetics*; D001682:Biological Availability; D002214:Capsules; D002851:Chromatography, High Pressure Liquid; D003106:Colon / Q000187:drug effects*; D004285:Dogs; D004305:Dose-Response Relationship, Drug; D016503:Drug Delivery Systems; D005079:Excipients / Q000494:pharmacology; D019695:Glycyrrhizic Acid / Q000008:administration & dosage / Q000493:pharmacokinetics*; D008297:Male; D011136:Polysorbates; D011312:Pressure; D013501:Surface-Active Agents / Q000494:pharmacology
D000890:Anti-Infective Agents; D002214:Capsules; D005079:Excipients; D011136:Polysorbates; D013501:Surface-Active Agents; D019695:Glycyrrhizic Acid