Preparation and rectal absorption of highly concentrated glycyrrhizin solution.
We developed a simple method for preparing a highly concentrated solution of glycyrrhizin monoammonium salt (GZ) at low viscosity with no surfactants nor organic solvents and investigated the absorption profile after rectal administration to rats. GZ (200 mg/ml) was dissolved in phosphate buffered solution, pH 7.0; over 350 mM concentration was maintained for the aqueous solution without gel-formation. When glycerin was used as a non-aqueous formulation, GZ did not form gel. Apparent permeability coefficients of GZ obtained from 350 mM phosphate buffered solution (pH 7.0) and glycerin solution through rat rectal mucosa estimated by in vitro parallel diffusion chamber technique were 0.686 x 10(-6) and 0.379 x 10(-6) cm/s, respectively. On the other hand, the area under plasma concentration-time curves of GZ in 400 mM phosphate buffer (pH 7.0) and glycerin formulations after rectal administration to the rat were significantly higher than that in polyethylene glycol 400/propylene glycol (55 : 5) formulation. Maximum plasma concentrations of these formulations were dependent on the apparent permeability coefficients of GZ. Increased absorption observed by phosphate buffered formulation accompanied no pronounced histological damage in mucosa. These results demonstrate that addition of a highly concentrated phosphate salts is effective not only for lowering the viscosity of a highly concentration of GZ solution, but also for improving the mucosal GZ absorption.
Koga
Kenjiro
K
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Hokuriku University, Kanazawa, Japan.
Kawashima
Susumu
S
Shibata
Nobuhito
N
Takada
Kanji
K
Murakami
Masahiro
M
D000285:Administration, Rectal; D000465:Algorithms; D000818:Animals; D000998:Antiviral Agents / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D001682:Biological Availability; D002021:Buffers; D055598:Chemical Phenomena; D002626:Chemistry, Pharmaceutical; D002627:Chemistry, Physical; D005782:Gels; D019695:Glycyrrhizic Acid / Q000008:administration & dosage / Q000737:chemistry / Q000493:pharmacokinetics*; D007408:Intestinal Absorption; D007420:Intestine, Large / Q000378:metabolism; D008297:Male; D019999:Pharmaceutical Solutions; D051381:Rats; D017208:Rats, Wistar; D012007:Rectum / Q000378:metabolism*; D012995:Solubility; D013696:Temperature; D013816:Thermodynamics
D000998:Antiviral Agents; D002021:Buffers; D005782:Gels; D019999:Pharmaceutical Solutions; D019695:Glycyrrhizic Acid