Self-Microemulsifying Drug Delivery System of Phillygenin: Formulation Development, Characterization and Pharmacokinetic Evaluation.

Lingzhi Wang,Jiankai Tang,Wenrui Yan,Liwei Zhang,Yurun Tian,Huanhuan Xue

doi:10.3390/pharmaceutics12020130

Lingzhi Wang, Jiankai Tang + Show 4 more

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https://doi.org/10.3390/pharmaceutics12020130

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Journal: Pharmaceutics	Publication Date: Feb 3, 2020
Citations: 26	License type: CC BY 4.0

Affiliation: Shanxi University

Abstract

Phillygenin, as an active ingredient of Forsythia suspensa, possesses a wide range of biological and pharmacological activity. However, its development and application are restricted due to its poor bioavailability and low solubility. Our work aimed to develop a self-microemulsifying drug delivery system to improve the oral bioavailability of phillygenin. The composition of the self-microemulsifying drug delivery system was preliminary screened by the pseudo-ternary phase diagram. Subsequently, the central composite design method was employed to optimize the prescription of the self-microemulsifying drug delivery system loaded with phillygenin. The prepared self-microemulsifying drug delivery system of phillygenin was characterized in terms of morphology, droplet size distribution, polydispersity index and stability. Then, the in vitro dissolution and the oral bioavailability were analyzed. The optimized self-microemulsifying drug delivery system of phillygenin consisted of 27.8% Labrafil M1944CS, 33.6% Cremophor EL, 38.6% polyethylene glycol 400 (PEG-400) and 10.2 mg/g phillygenin loading. The prepared self-microemulsifying drug delivery system of phillygenin exhibited spherical and uniform droplets with small size (40.11 ± 0.74 nm) and satisfactory stability. The in vitro dissolution experiment indicated that the cumulative dissolution rate of the self-microemulsifying drug delivery system of phillygenin was significantly better than that of free phillygenin. Furthermore, after oral administration in rats, the bioavailability of phillygenin was significantly enhanced by the self-microemulsifying drug delivery system. The relative bioavailability of the self-microemulsifying drug delivery system of phillygenin was 588.7% compared to the phillygenin suspension. These findings suggest that the self-microemulsifying drug delivery system of phillygenin can be a promising oral drug delivery system to improve the absorption of phillygenin.

Highlights

The fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae) is a well-known traditional Chinese medicine (TCM), named “Lianqiao” in Chinese
In order to increase the bioavailability of PG, the PG-self-microemulsifying drug delivery system (SMEDDS) formulation was developed
The appearance of the developed PG-SMEDDS was clear, and the microemulsion droplets were spherical in shape with an average size of 40.11 ± 0.74 nm

Summary

Introduction

The fruit of Forsythia suspensa (Thunb.) Vahl (Oleaceae) is a well-known traditional Chinese medicine (TCM), named “Lianqiao” in Chinese. It is distributed in China, Korea, Japan and many European countries [1]. Forsythia suspensa (F. suspensa) exhibits anti-bacterial, anti-inflammatory, antioxidant, anti-allergy, anti-virus and anti-cancer effects [2]. PG has provoked great interest due to its significant pharmacological activities, such as antioxidant, hypolipidemic [8], inhibition of tyrosinase activity [9] and anti-hypertensive effects [10]. Its remarkable ability to treat liver injury [11] and its anti-inflammatory properties have drawn great attention. Few studies have focused on improving the oral bioavailability of PG.

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Conclusion