Biopharmaceutical classification of Cimicifuga racemosa extract Ze 450

For classification of Cimicifuga racemosa extract Ze450 into the Biopharmaceutics classification system (BCS), up to four different substances of the main constituent class triterpene glycosides were selected to serve as analytical marker. The pH-dependent thermodynamic solubility was determined via shake-flask method and apparent permeability P_app was determined using Caco-2 monolayer assay. The solubility profiles of tested triterpene glycosides actein, 23-epi-26-deoxyactein, cimiracemosid C and 4-O-acetyl-hydroshengmanol-4-O-β-D-xylopyranosid showed pH dependent solubility with a maximum at pH 7.5 and a minimum at acidic pH values. In the scope of Caco-2 monolayer assay, 23-epi-26-deoxyactein was tested. It showed a high P_app (apparent permeability) from apical to basolateral which was found to be lower in the opposite direction. These findings imply a good uptake of 23-epi-26-deoxyactein associated with a low efflux transport. Due to the high solubility in combination with high permeability, triterpene glycosides can be classified into BCS class I. Furthermore, dissolution performance of a herbal medicinal product containing Cimicifuga racemosa extract Ze450 was assessed, using actein and 23-epi-26-deoxyactein as analytical marker. Both showed rapid dissolution according BCS criteria. The results suggest that dissolution is no critical step in liberation process of triterpene glycosides. Based on this assumption, good bioavailability of triterpene glycosides can be postulated. However, results allow no prediction of the bioavailability of the whole Cimicifuga racemosa extract Ze450.