인삼사포닌의 소장내 최종대사산물인 IH-901의 수용액중 가용화

Abstract

The purpose of the present study was to formulate the aqueous solution of 20-O-b-D-glucopyranosyl-20(S)-protopanaxadiol (IH-901), an intestinal bacterial metabolic derivative from Ginseng protopanaxadiol saponin. For this purpose, the effects of various solubilization agents such as cosolvents [ethanol, propylene glycol (PG), polyethylene glycol 300 (PEG 300), polyethylene glycol 400 (PEG 400), glycerin], surfactants (Tween 80, Cremophor RH40, Cremophor EL, Poloxamer 407, Poloxamer 188) and a complexation agent [hydroxypropyl-b-cyclodextrin (HPBCD)], on the solubility of IH-901 in aqueous solution were evaluated. The solubility of IH-901 in water was under 1mg/ml at 20oC. Cosolvents such as ethanol, PG, PEG 300, PEG 400 and glycerin did not enhance the solubility of IH-901 at the 0-40% concentration range. The solubility of IH-901 was significantly elevated by the addition of cosolvents over the 80% concentration range. On the other hand, tween 80, Cremophor EL, Cremophor RH40 and HPBCD showed enhanced effects on the solubility of IH-901. The enhanced effects of Poloxamer 407 or Poloxamer 188 on the IH-901 solubility were less pronounced compared with Cremophor EL or Cremophor RH40. As a results, Cremophor aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 10% Cremophor EL and 7% Cremophor RH40 were formulated as dosing solutions containing 5.0mg/ml of IH-901 for its intravenous and oral administration, respectively. The formular showed physical stability after stored for 7days at 4oC.