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Transcutol® P/Cremophor® EL/Ethyl Oleate–Formulated Microemulsion Loaded into Hyaluronic Acid–Based Hydrogel for Improved Transdermal Delivery and Biosafety of Ibuprofen

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Abstract

In the present study, a novel transdermal delivery system was developed and its advantages were demonstrated. Ibuprofen is a commonly used anti-inflammatory, antipyretic, and analgesic drug; however, because of its short biological half-life, it must be frequently administered orally and is highly irritating to the digestive tract. To prepare a novel transdermal delivery system for ibuprofen, a microemulsion was used as a drug carrier and dispersed in a hyaluronic acid-based hydrogel (ME/Gel) to increase percutaneous drug absorption while avoiding gastrointestinal tract irritation. The prepared microemulsion had a droplet size of ~ 90 nm, and the microemulsion had good stability in the hydrogel. Rheological tests revealed that the ME/Gel is a pseudoplastic fluid with decreased viscosity and increased shear rate. It displayed a certain viscoelasticity, and the microemulsion distribution displayed minor effects on the rheological characteristics of the hydrogel system. There was no significant difference in the rheology of the ME/Gel at 25°C and 32°C (normal skin surface temperature), which is beneficial for clinical application. Drug transdermal flux was significantly higher than that of the hydrogel and commercial cream groups (p < 0.01). The 24-h cumulative drug permeation amount was 1.42-fold and 2.52-fold higher than that of the hydrogel and cream groups, respectively. By loading into the ME/Gel, the cytotoxicity of the drug to HaCaT cells was reduced. These results indicate that the prepared ME/Gel can effectively improve transdermal ibuprofen delivery and the biosafety of the drug and could therefore have applicability as a drug delivery system.

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Abbreviations

IBU:

Ibuprofen

HA:

Hyaluronic acid

ME:

Ibuprofen-loaded microemulsion

ME/Gel:

Ibuprofen-loaded microemulsion-based hyaluronic acid hydrogel

Gel:

Ibuprofen-loaded hyaluronic acid hydrogel

NS:

Normal saline

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Contributions

All authors contributed to the experimental studies, data collection and statistical analysis, and the structuring and writing of the article.

Availability of Data and Materials

The data used to derive Fig. 3 and Fig. 5b in this work can be obtained upon reasonable request from the corresponding author.

Funding

This work was financially supported by the National Natural Science Foundation of China (81673612, 81573619).

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Author notes

  1. Yongtai Zhang, Kai Zhang and Zhi Wang contributed equally to this work.

Authors and Affiliations

  1. Department of Pharmaceutical Sciences, Shanghai University of Traditional Chinese Medicine, Shanghai, 201203, China

    Yongtai Zhang, Kai Zhang, Zhi Wang, Hongmei Hu, Qian Jing, Yanyan Li, Teng Guo & Nianping Feng

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  1. Yongtai Zhang
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  2. Kai Zhang
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Correspondence to Nianping Feng.

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The study protocol was approved by the Experimental Animal Ethics Committee of Shanghai University of Traditional Chinese Medicine (License No. SYXK (HU) 2014-0008).

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Zhang, Y., Zhang, K., Wang, Z. et al. Transcutol® P/Cremophor® EL/Ethyl Oleate–Formulated Microemulsion Loaded into Hyaluronic Acid–Based Hydrogel for Improved Transdermal Delivery and Biosafety of Ibuprofen. AAPS PharmSciTech 21, 22 (2020). https://doi.org/10.1208/s12249-019-1584-8

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