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Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology

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ABSTRACT

Purpose

To achieve controlled release of integral nanoparticles by the osmotic pump strategy using nanostructured lipid carriers (NLCs) as model nanoparticles.

Methods

NLCs was prepared by a hot-homogenization method, transformed into powder by lyophilization, and formulated into osmotic pump tablets (OPTs). Release of integral NLCs was visualized by live imaging after labeling with a water-quenching fluorescent probe. Effects of formulation variables on in vitro release characteristics were evaluated by measuring the model drug fenofibrate. Pharmacokinetics were studied in beagle dogs using the core tablet and a micronized fenofibrate formulation as references.

Results

NLCs are released through the release orifices of the OPTs as integral nanoparticles. Near zero-order kinetics can be achieved by optimizing the influencing variables. After oral administration, decreased C max and steady drug levels for as long as over 24 h are observed. NLC-OPTs show an oral bioavailability of the model drug fenofibrate similar to that of the core tablets, which is about 1.75 folds that of a fast-release formulation.

Conclusion

Controlled release of integral NLCs is achieved by the osmotic pump strategy.

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Abbreviations

ACQ:

Aggregation-caused quenching

ARE:

Average radiant efficiency

ATO5:

Precirol ATO® 5

FA:

Fenofibric acid

FNB:

Fenofibrate

GI:

Gastrointestinal

NLCs:

Nanostructured lipid carriers

OPTs:

Osmotic pump tablets

PDI:

Polydispersity index

PEG:

Polyethylene glycol

PEO:

Polyox™ WSR N80

PVP:

Polyvinylpyrrolidone

TEM:

Transmission electron microscopy

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ACKNOWLEDGMENTS AND DISCLOSURES

This study was financially supported by Shanghai Commission of Science and Technology (14JC1490300), National Natural Science Foundation of China (81573363, 81001405), and National Key Basic Research Program (2015CB931800). The authors declare no potential conflicts of interest.

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Author notes

    Authors and Affiliations

    1. School of Pharmacy, Key Laboratory of Smart Drug Delivery of MOE and PLA, Fudan University, Shanghai, 201203, China

      Zhiqiang Tian, Qin Yu, Yunchang Xie, Yi Lu, Xiaochun Dong, Weili Zhao, Jianping Qi & Wei Wu

    2. Department of Pharmacy, Shanghai Xuhui Dahua Hospital, Shanghai, China

      Fengqian Li

    3. Key Laboratory for Special Functional Materials of the Ministry of Education, Henan University, Kaifeng, China

      Weili Zhao

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    1. Zhiqiang Tian
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    Correspondence to Jianping Qi or Wei Wu.

    Additional information

    Zhiqiang Tian and Qin Yu contributed equally to this work.

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    Tian, Z., Yu, Q., Xie, Y. et al. Controlling Release of Integral Lipid Nanoparticles Based on Osmotic Pump Technology. Pharm Res 33, 1988–1997 (2016). https://doi.org/10.1007/s11095-016-1935-z

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    • DOI: https://doi.org/10.1007/s11095-016-1935-z

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