Pharmaceutical Nanotechnology
A High-Drug-Loading Self-Assembled Nanoemulsion Enhances the Oral Absorption of Probucol in Rats

https://doi.org/10.1002/jps.23460Get rights and content

ABSTRACT

The purpose of this study was to develop a high-drug-loading nanoemulsion by self-assembly to improve the oral absorption of high dosing poorly water-soluble drugs. Probucol was selected as a model drug and the probucol-loaded self-assembled nanoemulsion (PSN) was prepared and characterized. Moreover, the intestinal absorption and in vivo pharmacokinetic behavior of PSN were evaluated in rats after oral administration. The experimental results indicated that PSN was nanometer-sized droplets with the mean diameter of 40.32 ± 0.31 nm and polydispersity index of 0.184 ± 0.005. The aqueous solubility of probucol was remarkably increased after its incorporation into PSN. Compared with free drug suspension, the intestinal absorption of PSN was not significantly increased in duodenum, but obviously enhanced 3.62- and 13.1-fold in jejunum and ileum, respectively. In particular, the in vivo pharmacokinetic results indicated that the oral bioavailability of probucol was greatly improved 8.97-fold by PSN.

Thereby, the high-drug-loading self-assembled nanoemulsion was very effective in enhancing the oral absorption of high-dosing poorly water-soluble drugs.

Section snippets

INTRODUCTION

With few exceptions, the effectiveness of orally administrated drugs significantly depends on their systemic exposure following oral delivery.1 However, approximately 30% of commercial drugs and 40% of new drug candidates are poorly soluble in water and exhibit too low oral bioavailability, which present the major hurdles to their clinical application.2., 3. Alternatively, many poorly water-soluble drugs have to be administered with higher dose to achieve the therapeutic efficacy.4., 5.

Materials

Probucol (purity 99.7%) was purchased from Wuyi Ci- hang Pharmaceutical Company Ltd. (Hebei, China). Solutol®HS-15 was obtained from BASF (Ludwigshafen, Germany) and medium-chain triglycerides (MCTs) were kindly gifted by Gattefosse (Saint Priest Cedex, France). Tween 80 was provided by the Sinopharm Chemical Reagent Company Ltd. (Shanghai, China). All other chemicals and solvents were of analytical or high-performance liquid chromatography (HPLC) grade.

Preparation of PSN

Probucol, Solutol®HS-15 (BASF), MCT, and

Preparation and Characterization of PSN

Self-assembled nanoemulsion (SN) was designed to improve the oral absorption of poorly water-soluble drugs with high dosing. The hydrophobic drugs could be entrapped into the lipophilic core of nanoemulsion consisting of oil and hydrophobic part of surfactant and stabilized with the hydrophilic surface, which could be effective to improve the aqueous solubility and oral absorption of poorly water-soluble drugs.14 In the present study, probucol was loaded into the SN with a high drug loading of

CONCLUSIONS

A high-drug-loading SN was developed to improve the oral absorption of poorly water-soluble probucol with high dosing. The PSN was homogeneous nanometersized droplets with the mean diameter of 40.32 ± 0.31 nm. The aqueous solubility of probucol was remarkably increased after its incorporation into PSN. Compared with free probucol suspension, the intestinal absorption of PSN was not significantly enhanced in duodenum, but obviously increased 3.62- and 13.1- fold in jejunum and ileum, respectively.

ACKNOWLEDGMENTS

The National Basic Research Program of China (2009CB930304, 2013CB932503, and 2013CB932704), Shanghai Rising-Star Program (11QA1407900), and SA-SIBS Scholarship Program are gratefully acknowledged for financial support.

REFERENCES (25)

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Zhiwen Zhang and Jian Huang contributed equally to this work.

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