Solubilization of IH-901, a Novel Intestinal Metabolite of Ginseng Saponin, in Aqueous Solution

The purpose of the present study was to formulate the aqueous solution of $20-O-{\beta}-D-glucopyranosyl-20(S)-protopanaxadiol\;(IH-901)$, 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 $(Tween\;80,\;Cremophor^{\circledR}\;RH40,\;Cremophor^{\circledR}\;EL,\;Poloxamer\;407,\;Poloxamer\;188)$ and a complexation agent $[hydroxypropyl-{\beta}-cyclodextrin\;(HPBCD)]$, on the solubility of IH-90l in aqueous solution were evaluated. The solubility of IH-901 in water was under $1\;{\mu}g/ml\;at\;20^{\circ}C$. 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, $Cremophor^{\circledR}\;EL,\;Cremophor^{\circledR}\;RH40$ 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 $Cremophor^{\circledR}\;EL\;or\;Cremophor^{\circledR}\;RH40$. As a results, $Cremophor^{\circledR}$ aqueous solution was selected as an optimum solvent system. The aqueous solutions containing 10% $Cremophor^{\circledR}\;EL$ and 7% $Cremophor^{\circledR}\;RH40$ were formulated as dosing solutions containing 5.0 mg/ml of IH-901 for its intravenous and oral administration, respectively. The formular showed physical stability after stored for 7 days at $4^{\circ}C$.

인삼사포닌의 소장내 최종대사물인 IH-901의 수용액중 가용화