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Preparation of Ondansetron Hydrochloride-Loaded Nanostructured Lipid Carriers Using Solvent Injection Method for Enhancement of Pharmacokinetic Properties

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Abstract

Purpose

This study aimed to incorporate ondansetron hydrochloride (ODS), a water-soluble drug into nanostructured lipid carriers (NLCs) to improve the pharmacokinetic properties of the drug.

Methods

NLCs were produced by solvent injection method. Various parameters of formulation and process were assessed to enhance the drug incorporation into NLCs. Physicochemical analyses, in vitro drug release, and pharmacokinetic studies were performed.

Results

Entrapment efficiency (EE) of ODS was considerably improved (>90%) by increasing pH of the aqueous phase. The use of an appropriate level of liquid lipid resulted in small, monodispersed NLCs with the enhanced EE and drug loading (DL). The optimized NLCs formulation exhibited particle size of 185.2 ± 1.9 nm, polydispersity index of 0.214 ± 0.006, EE of 93.2 ± 0.5%, and DL of 10.43 ± 0.05% as well as an in vitro sustained-release profile of ODS. Differential scanning calorimetry and X-ray powder diffraction suggested the amorphous state of ODS in the NLCs. The pharmacokinetic study in rats exhibited the sustained-release characteristic of the optimized ODS-loaded NLCs following subcutaneous administration with an extended Tmax and mean residence time as well as the enhanced systemic exposure compared to the ODS solution.

Conclusions

The ODS-loaded NLCs appear potential for prolongation of drug action and reduction in dosing frequency.

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Abbreviations

CINV:

Chemotherapy-induced nausea and vomiting

DL:

Drug loading

DSC:

Differential scanning calorimetry

EE:

Entrapment efficiency

FTIR:

Fourier transform-infrared spectroscopy

HPLC:

High performance liquid chromatography

IS:

Internal standard

LC-MS/MS:

Liquid chromatography – tandem mass spectroscopy

MRM:

Multiple reaction monitoring

MRT:

Mean residence time

MWCO:

Molecular weight cut-off

NLCs:

Nanostructured lipid carriers

ODS:

Ondansetron hydrochloride

SLNs:

Solid lipid nanoparticles

TEM:

Transmission electron microscopy

XRD:

X-ray powder diffraction

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Acknowledgments and disclosures

All authors declare that they have no conflict of interest to disclose.

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Authors and Affiliations

  1. College of Pharmacy, Gachon University, 191 Hambakmoero, Yeonsu-gu, Incheon, 21936, South Korea

    Van-An Duong, Thi-Thao-Linh Nguyen, Han-Joo Maeng & Sang-Cheol Chi

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  1. Van-An Duong
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  2. Thi-Thao-Linh Nguyen
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Correspondence to Sang-Cheol Chi.

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Duong, VA., Nguyen, TTL., Maeng, HJ. et al. Preparation of Ondansetron Hydrochloride-Loaded Nanostructured Lipid Carriers Using Solvent Injection Method for Enhancement of Pharmacokinetic Properties. Pharm Res 36, 138 (2019). https://doi.org/10.1007/s11095-019-2672-x

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