Now there are few good oral preparations of puerarin used in cerebrovascular diseases because of its poor oral absorption caused by the low water solubility and the poor penetration into brain. In this study, three oral formulations of puerarin, nanocrystals suspension (NCS), inclusion compounds solution (ICS) and self-microemulsifying drug delivery system (SMEDDS) were prepared with borneol as an oral brain-targeting enhancer. A rat syngeneic in vitro model of the brain–blood barrier (BBB) was established to investigate effects of borneol on the permeability of puerarin across the BBB. The pharmacokinetics of puerarin in mice after oral administration was investigated by a high performance liquid chromatography-mass spectrometry/mass spectrometry (HPLC-MS/MS) method. The in vitro BBB model study showed the permeability of puerarin was increased significantly (p < 0.05) and the value of transepithelial electrical resistance at 2 h was decreased significantly (p < 0.01) when the concentration of borneol was over 12.5 μg/mL compared with the control group. The pharmacokinetics results indicated borneol with doses of over 50 mg/kg could obviously increase both intestinal absorption and brain penetration of puerarin. With co-administration of borneol (100 mg/kg), the AUC of puerarin both in plasma (AUC_plasma) and in brain (AUC_brain) for SMEDDS were significantly higher than those for NCS (p < 0.01) and ICS (p < 0.05). These results suggested borneol in combination with SMEDDS could improve both the oral absorption and the brain penetration of puerarin in mice, which was promising for the development of an oral formulation of puerarin used in cerebrovascular diseases.

In this study, an oral drug nanocrystals self-stabilized Pickering emulsion (NSSPE), which used nanocrystals of a poorly soluble ingredient from Puerariae Radix called puerarin as solid particle stabilizers and Ligusticum chuanxiong essential oil since the main oil phase had been developed to improve the oral bioavailability of puerarin. The appearance of emulsions, size and zeta potential of droplets, and content of puerarin in emulsified layer during a storage of six months at 4, 25, and 40 °C were investigated. The centrifugation stability at 4000× g was also studied. The micro-structure of emulsion droplets was characterized by a scanning electron micrograph (SEM), confocal laser scanning microscopy (CLSM), a fluorescence microscope (FM), and differential scanning calorimetry (DSC). The in vivo oral bioavailability of puerarin NSSPE was investigated in rats. Results showed that appearances of puerarin NSSPE kept stable after centrifugation at 4000× g for 15 min or storage for six months at 4, 25, and 40 °C. SEM, CLSM, FM, and DSC showed that the puerarin NSSPE had a stable core-shell structure of emulsion droplets formed by the adsorption of puerarin nanocrystals on the surface of oil droplets of mixed oil of Ligusticum chuanxiong essential oil and Labrafil M 1944 CS (9:1, v/v). The relative bioavailability of puerarin NSSPE to puerarin coarse powder suspension, nanocrystal suspension, and surfactant emulsion were 262.43%, 155.92%, and 223.65%, respectively. All these results indicated that puerarin nanocrystals could stabilize Pickering emulsion of Ligusticum chuanxiong essential oil without any other stabilizers and Pickering emulsion could improve the oral bioavailability of puerarin, which suggests that the drug nanocrystal self-stabilized Pickering emulsion as a promising oral drug delivery system for Traditional Chinese Medicine containing poorly soluble ingredients and volatile oils.

Self-microemulsifying drug delivery systems (SMEDDS) offer potential for improving the oral bioavailability of poorly water-soluble drugs. However, their susceptibilities during long term storage and in vivo precipitation issues limit their successful commercial application. To overcome these limitations, SMEDDS can be solidified with solid carriers, thus producing solid self-microemulsifying drug delivery systems (S-SMEDDS). In this study, effects of various hydrophilic carriers on structural transitions and in vitro properties of S-SMEDDS were investigated in order to set up in vitro methods for screening out appropriate carriers for S-SMEDDS. Liquid SMEDDS was prepared and characterized using nimodipine as a model drug. The effects of various hydrophilic carriers on internal microstructure and solubilization of SMEDDS were investigated by conductivity measurement and in vitro dispersion test. The results showed that hydrophilic carriers including dextran 40, maltodextrin and PVP K30 seemed to delay the percolation transition of SMEDDS, allowing it to maintain a microstructure that was more conducive to drug dissolution, thus significantly increasing the solubilization of nimodipine in the self-microemulsifying system and decreasing drug precipitation when dispersed in simulated gastric fluid. S-SMEDDS of nimodipine were prepared by using spray drying with hydrophilic carriers. The effects of various hydrophilic carriers on in vitro properties of S-SMEDDS were investigated by using SEM, DSC, PXRD and in vitro dissolution. The results showed that properties of hydrophilic carriers, especially relative molecular mass of carriers, had obvious influences on surface morphologies of S-SMEDDS, reconstitution of microemulsion and physical state of nimodipine in S-SMEDDS. Considering that in vitro properties of S-SMEDDS are closely related to their pharmacokinetic properties in vivo, the simple and economical in vitro evaluation methods established in this paper can be used to screen solid carriers of S-SMEDDS well.

A drug nanocrystal self-stabilized Pickering emulsion (DNSPE) is a novel Pickering emulsion with drug nanocrystals as the stabilizer. As a promising drug delivery system, DNSPEs have attracted increasing attention in recent years due to their high drug loading capacity and ability to reduce potential safety hazards posed by surfactants or specific solid particles. This paper comprehensively reviews the progress of research on DNSPEs, with an emphasis on the main factors influencing their construction, characteristics and measurement methods in vitro, and fate in vivo, and puts forward issues that need to be studied further. The review contributes to the advancement of DNSPE research and the promotion of their application in the field of drug delivery.

A drug nanocrystals self-stabilized Pickering emulsion (NSSPE) with a unique composition and microstructure has been proven to significantly increase the bioavailability of poorly soluble drugs. This study aimed to develop a new solid NSSPE of puerarin preserving the original microstructure of NSSPE by spray-drying. A series of water-soluble solid carriers were compared and then Box-Behnken design was used to optimize the parameters of spray-drying. The drug release and stability of the optimized solid NSSPE in vitro were also investigated. The results showed that hydroxypropyl-β-cyclodextrin (HP-β-CD), rather than solid carriers commonly used in solidification of traditional Pickering emulsions, was suitable for the solid NSSPE to retain the original appearance and size of emulsion droplets after reconstitution. The amount of HP-β-CD had more influences on the solid NSSPE than the feed rate and the inlet air temperature. Fluorescence microscopy, confocal laser scanning microscopy and scanning electron microscopy showed that the reconstituted emulsion of the solid NSSPE prepared with HP-β-CD had the same core-shell structure with a core of oil and a shell of puerarin nanocrystals as the liquid NSSPE. The particle size of puerarin nanocrystal sand interfacial adsorption rate also did not change significantly. The cumulative amount of released puerarin from the solid NSSPE had no significant difference compared with the liquid NSSPE, which were both significantly higher than that of puerarin crude material. The solid NSSPE was stable for 3 months under the accelerated condition of 75% relative humidity and 40 °C. Thus, it is possible todevelop the solid NSSPE preserving the unique microstructure and the superior properties in vitro of the liquid NSSPE for poorly soluble drugs.