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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) is prepared by wet media milling. The stabilizers Aerosi and SDS are used to formulate TFE‐PLC nanosuspensions (TFE‐PLC–Ns) to improve the dispersion of TFE–PLC. FTIR and DSC data confirms the formation of TFE‐PLC. The oil solubility of ICA and ICA II in the complex in octanol is improved nearly four times over that in TFE. The logP of ICA in TFE‐PLC is significantly increased with a value from 1.61 to 2.02 at pH 4.5, and ICA II, from 3.24 to 4.77. The mean diameter of the TFE‐PLC‐Ns is reduced from 6.166 to 0.424 μm, and its dissolution is improved over TFE. In the in vivo evaluation, TFE‐PLC‐Ns exhibits a considerable enhancement with larger AUC0–t and shorter Tmax than TFE and TFE‐PLC. The relative bioavailability of ICA in TFE‐PLC and TFE‐PLC‐Ns are 181.75 and 249.05%, respectively, and for ICA II 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 ICA II in TFE are very low due to their poor lipophilicity and cell permeability. Here, TFE‐PLC‐Ns is proposed, which is prepared by wet media milling for improving lipophilic properties and oral bioavailability. In addition, some proofs of TFE‐PLC are investigated in detail, and TFE‐PLC‐Ns significantly increased the oral bioavailability of ICA and ICA II in TFE. Therefore, the authors recommend a potential drug vehicle of TFE‐PLC‐Ns for oral administration of ICA and ICA II, and a novel method of phospholipid complex preparation for industrial manufacture. In this article, the total flavonoids of epimedium–phospholipid complex (TFE‐PLC) is prepared to enhance the lipophilicity of icariin (ICA) and icariside II (ICA II) in TFE. Aerosi and SDS are used to formulate TFE‐PLC nanosuspensions (TFE‐PLC‐Ns) to improve the dispersion of TFE‐PLC. And finally, TFE‐PLC‐Ns exhibits enhanced oral bioavailability of ICA and ICA II compared with them in TFE and TFE‐PLC. [ABSTRACT FROM AUTHOR]

The aim of this study was to improve the oral bioavailability of a practically insoluble drug, efonidipine hydrochloride (EFH), by agglomeration in acid solution/gastric fluid. The EFH nanosuspension was prepared by the wet-milling method with F68 as a dispersing agent, SDS as an auxiliary stabilizer and l -arginine as a pH adjusting agent. The EFH nanosuspension have been prepared in industrial scale-up. The dissolution rate of the EFH nanosuspension was greater than that of bulk EFH. An in vitro intestinal permeability study showed a clear increase in the apparent permeability of different intestinal segments compared with bulk EFH. Also, a pharmacokinetic study showed that the C max and AUC 0-24h of the nanosuspensions were approximately 1.76-fold and 2.2-fold greater than that of bulk EFH, respectively, and there was no significant difference compared with commercial tablets. It appears that wet-milling offers an effective approach to improve the dissolution rate and oral absorption of this practically insoluble drug. [ABSTRACT FROM AUTHOR]

Abstract: The aim of this study was to prepare and characterize nitrendipine nanosuspensions to enhance the dissolution rate and oral bioavailability of this drug. Nanosuspensions were prepared by the precipitation–ultrasonication method. The effects of five important process parameters, i.e. the concentration of PVA in the anti-solvent, the concentration of nitrendipine in the organic phase, the precipitation temperature, the power input and the time length of ultrasonication on the particle size of nanosuspensions were investigated systematically, and the optimal values were 0.15%, 30mg/ml, below 3°C, 400W and 15min, respectively. The particle size and zeta potential of nanocrystals were 209nm (±9nm) and −13.9mV (±1.9mV), respectively. The morphology of nanocrystals was found to be flaky in shape by scanning electron microscopy (SEM) observation. The X-ray powder diffraction (XRPD) and differential scanning calorimetry (DSC) analysis indicated that there was no substantial crystalline change in the nanocrystals compared with raw crystals. The in vitro dissolution rate of nitrendipine was significantly increased by reducing the particle size. The in vivo test demonstrated that the C max and AUC0→12 values of nanosuspension in rats were approximately 6.1-fold and 5.0-fold greater than that of commercial tablets, respectively. [Copyright &y& Elsevier]