Ginsenoside CK-loaded self-nanomicellizing solid dispersion with enhanced solubility and oral bioavailability.

ABSTRACT

Ginsenoside compound K (CK) is a major ginsenoside metabolite of protopanaxadiol, which exhibits numerous pharmacological activity such as cardioprotective and antidiabetic. However, the therapeutic application of CK is hampered by its physicochemical characteristics and low oral bioavailability (BA). The present work aims at the preparation of CK to improve its dissolution and enhance the oral BA for the management of arrhythmia by using self-nanomicellizing solid dispersion system (SSD). The formulations were characterized by advanced techniques like DSC, XRD, FTIR, SEM and XRD. In the in vivo pharmacokinetic study, UPLC-MS/MS was used to measure the concentration of CK in plasma. Mapping Lab was applied in the experiment of perfused intact hearts to determine the ventricular rate and ventricular conduction velocity. The solubility of CK-SSD8 was 4658.11 ± 6.66 µg/ml, which is 130-fold than free CK, and the dissolution rate was faster than any other dosage forms. The average diameters of CK-SSD were smaller than 100 nm. The in vivo pharmacokinetic study revealed that the AUC(0-24) of CK-SSD8 formulation was 2.02-fold higher than pure CK. Moreover, the study performed to evaluate the efficiency in arrhythmia treatment showed a reduced ventricular rate and ventricular conduction velocity. Thus, CK-SSD could serve as potential carrier candidate in improving the clinical application of CK.