Preparation and Characterization of Loperamide-Loaded Dynasan 114 Solid Lipid Nanoparticles for Increased Oral Absorption In the Treatment of Diarrhea.

Lili Wei,Kun Shi,Yunfang Yang,Jingxin Mo,Jun Wu,Wei Zhao

doi:10.3389/fphar.2016.00332

Abstract

The aim of the project was to assemble two optimum solid lipid nanoparticle (SLN) formulations for oral delivery of loperamide (LPM) to treat different types of diarrhea, and to evaluate their release profiles in vitro and pharmacokinetic properties in vivo. In this work, glyceryl trimyristate (Dynasan 114) nanoparticles containing the drug LPM and sodium cholate as a stabilizer were prepared using a modified solvent evaporation technique. Two LPM-loaded SLNs, namely LPM-SLN-1 (LPM-SLN with a high ratio rate of lipid to drug) and LPM-SLN-2 (LPM-SLN with a low ratio rate of lipid to drug), were prepared by the solvent evaporation method. A change in the lipid concentration affects the characteristics of LPM-SLNs. The average sizes of the LPM-SLNs were 303 ± 18 nm and 519 ± 36 nm, separately, as analyzed by dynamic light scattering. The LPM-SLNs were found to be round with a smooth surface, as observed using a transmission electron microscope and a scanning electron microscope. The average encapsulation efficiencies were 87 ± 3.78% w/w and 84 ± 5.17%, accordingly. In the in vitro release experiments, LPM-SLNs showed a continuous release profile of LPM without any burst release. The oral bioavailability of LPM-SLNs was analyzed using Wistar rats. The relative bioavailabilities of LPM-SLNs were 227 and 153%, respectively, as compared that of the LPM tablet. There was no difference in the Tmax between LPM-SLN-2 and the LPM tablet. In conclusion, LPM-SLN-1 significantly improved the oral bioavailability of LPM, while LPM-SLN-2 having the same swift action as the LPM tablet. These results demonstrate the potential of LPM-SLNs in the oral delivery of LPM to treat different types of diarrhea.

Highlights

Loperamide (LPM) is an orally administered antidiarrheal agent indicated for the short-term treatment of acute and chronic diarrhea in adults (Natalja et al, 2013)
The dynamic light scattering (DLS) measurements for LPM-solid lipid nanoparticle (SLN)-1 showed a mean size of 303 ± 18 nm, with a polydispersity index (PDI) of 0.19 ± 0.01
zeta potential (ZP) measurements suggested that LPM-SLN-1 possessed a high negative surface charge of −47.33 ± 4.29 mV

Summary

Introduction

Loperamide (LPM) is an orally administered antidiarrheal agent indicated for the short-term treatment of acute and chronic diarrhea in adults (Natalja et al, 2013). LPM is available in a range of orally administered formulations, including tablets, capsules, a combination chewable tablet, and an orodispersible formulation (Trottet et al, 2004). LPM has limitations in oral administration owing to its extreme bitter taste. Its slow dissolution rate in the intestinal tract and its significant first-pass effect largely restrict its clinical use (Trottet et al, 2004). To overcome these challenges, Ueda and Kreuter (1997) had successfully loaded LPM into Poly(L-lactide) nanoparticles to increase its solubility and to improve its release profile in vitro (Ueda and Kreuter, 1997). There are few reports on the formulation of LPM solid lipid nanoparticles (SLNs), which could be a possible way to overcome the limitations in the oral absorption of LPM

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