Phospholipid complex of ICA and ICAII prepared by wet media milling for improving bioavailability

Abstract

In order to enhance the lipophilicity and thus oral bioavailability of Icariin (ICA) and Icariside II (ICA II) of Total Flavonoids of Epimedium (TFE), a Total Flavonoids of Epimedium-phospholipid complex (TFE–PLC) was prepared by wet media milling. The stabilizers Aerosi and SDS were used to formulate TFE-PLC nanosuspensions (TFE-PLC-Ns) to improve the dispersion of TFE-PLC. FTIR and DSC data confirmed the formation of TFE–PLC. The oil solubility of ICA and ICAII in the complex in octanol was improved nearly 4 times over that in TFE. The logP of ICA in TFE-PLC was significantly increased with a value from 1.61 to 2.02 at pH 4.5, and ICAII, from 3.24 to 4.77. The mean diameter of the TFE-PLC-Ns was reduced from 6.166 to 0.424 µm, and its dissolution was improved over TFE. In the in vivo evaluation, TFE-PLC-Ns exhibited a considerable enhancement with larger AUC_0-t and shorter T_max than TFE and TFE-PLC. The ralative bioavailability of ICA in TFE-PLC and TFE-PLC-Ns are 181.75% and 249.05%, respectively, and for ICAII are 401.63% and 684.70%, respectively. Therefore it suggests that TFE-PLC-Ns has possibilities in enhancing oral bioavailability of TFE, which may be due to its improved lipophilicity and wettability.

Practical applications: The oral bioavailability of ICA and ICAII in TFE are very low due to their poor lipophilicity and cell permeability. Here we propose TFE-PLC-Ns, which is prepared by wet media milling for improving lipophilic properties and oral bioavailability. In addition, some proofs of TFE-PLC were investigated in detail, and TFE-PLC-Ns significantly increased the oral bioavailability of ICA and ICAII in TFE. Therefore, we recommend a potential drug vehicle of TFE-PLC-Ns for oral administration of ICA and ICAII, and a novel method of phospholipid complex preparation for industrial manufacture.

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