A Novel Solid Nanocrystals Self-Stabilized Pickering Emulsion Prepared by Spray-Drying with Hydroxypropyl-β-cyclodextrin as Carriers.

Jifen Zhang,Yanhua Wang,Jirui Wang,Tao Yi

doi:10.3390/molecules26061809

Abstract

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.

Highlights

The low bioavailability is a great challenge for oral administration of poorly watersoluble drugs, such as puerarin, silybin and so on
It was found that solid nanocrystals self-stabilized Pickering emulsion (NSSPE) prepared with the most commonly used solid carriers in spray drying of emulsions, such as starch dextrin, maltodextrin, mannitol and lactose, all showed poor reconstitution
The droplet sizes of reconstituted emulsions from these solid NSSPE increased significantly and were 4.82, 7.84, 2.32 and 6.80 times that of the liquid NSSPE, respectively. This may be because that these solid carriers could not protect the microstructure of the liquid NSSPE during spray drying. It was difficult for the oil in these solid NSSPE powders to be dispersed uniformly without sufficient energy provided by high pressure homogenization when re-dispersed in water

Summary

Introduction

The low bioavailability is a great challenge for oral administration of poorly watersoluble drugs, such as puerarin, silybin and so on. A novel liquid Pickering emulsion with a unique composition and microstructure, i.e., drug nanocrystals self-stabilized Pickering emulsion (NSSPE) has been developed to orally deliver poorly water-soluble drugs. In NSSPE, nanocrystals of poorly water-soluble drugs, which acted as the therapeutic substance as well as the stabilizer of emulsion, were adsorbed at the oil-water interface, forming a unique core-shell structure with a core of oil saturated with drug and a shell of drug nanocrystals [1,2]. NSSPE could significantly enhance the oral bioavailability of poorly water-soluble drugs. Pharmacokinetics studies showed NSSPE improved AUC of silybin and puerarin to 4.6 times and 2.6 times compared with crude material, respectively [1,2], suggesting great application potential for oral administration of poorly water-soluble drugs. NSSPE has the higher drug loading and safety than traditional emulsions [3,4]

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Conclusion