The role of lipid-based nano delivery systems on oral bioavailability enhancement of fenofibrate, a BCS II drug: comparison with fast-release formulations.

Tengfei Weng,Zongning Yin,Kaili Hu,Yi Lu,Jianping Qi,Zhiqiang Tian,Wei Wu,Kai Wang

doi:10.1186/s12951-014-0039-3

Abstract

The aim of this study was to compare various formulations solid dispersion pellets (SDP), nanostructured lipid carriers (NLCs) and a self-microemulsifying drug delivery system (SMEDDS) generally accepted to be the most efficient drug delivery systems for BCS II drugs using fenofibrate (FNB) as a model drug. The size and morphology of NLCs and SMEDDS was characterized by dynamic light scattering (DLS) and transmission electron microscopy (TEM). Their release behaviors were investigated in medium with or without pancreatic lipase. The oral bioavailability of the various formulations was compared in beagle dogs using commercial Lipanthyl® capsules (micronized formulation) as a reference. The release of FNB from SDP was much faster than that from NLCs and SMEDDS in medium without lipase, whereas the release rate from NLCs and SMEDDS was increased after adding pancreatic lipase into the release medium. However, NLCs and SMEDDS increased the bioavailability of FNB to 705.11% and 809.10%, respectively, in comparison with Lipanthyl® capsules, although the relative bioavailability of FNB was only 366.05% after administration of SDPs. Thus, lipid-based drug delivery systems (such as NLCs and SMEDDS) may have more advantages than immediate release systems (such as SDPs and Lipanthyl® capsules).

Highlights

According to the definition of the Biopharmaceutics Classification System (BCS) proposed by Amidon in 1995, both BCS II and IV drugs are poorly soluble in aqueous solution [1]
Each drug delivery system may be recognized to improve oral bioavailability of poorly soluble drugs, we aimed to identify the optimal formulation technology for delivery of BCS II or IV drugs
Since FNB-loaded solid dispersion pellets (SDP) and nanostructured lipid carriers (NLCs) were prepared according to our previous study [25,26], the detailed characterization data are not shown in this report

Summary

Introduction

According to the definition of the Biopharmaceutics Classification System (BCS) proposed by Amidon in 1995, both BCS II and IV drugs are poorly soluble in aqueous solution [1]. About 40% of new drug candidates identified by chemical screening are poorly soluble in water (BCS II or IV drugs), which greatly hinders their translation into the clinic [2]. Digestion products of lipid nanoparticles can solubilize lipophilic drugs and the presence of endogenous bile salts may alter the intrinsic permeability of the intestinal membrane [19,20]. Each drug delivery system may be recognized to improve oral bioavailability of poorly soluble drugs, we aimed to identify the optimal formulation technology for delivery of BCS II or IV drugs. In this study, we first compared the bioavailability of different drug delivery systems loaded with the BCS II drug, fenofibrate (FNB)

Objectives

Methods

Results

Conclusion