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Ketoprofen Microemulsion for Improved Skin Delivery and In Vivo Anti-inflammatory Effect

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Abstract

We have designed a microemulsion (ME) containing Ketoprofen (KET) for anti-inflammatory effect evaluated using the rat paw edema model. The ME was prepared by adding propylene glycol (PG) loaded with 1% KET/water (3:1, w/w), to a mixture of sorbitan monooleate and polysorbate 80 (47.0%) at 3:1 (w/w) and canola oil (38.0%). The physicochemical characterization of KET-loaded ME involved particle size and zeta potential determination, entrapment efficiency, calorimetric analysis, and in vitro drug release. The in vivo anti-inflammatory study employed male Wistar rats. Measurement of the foot volume was performed using a caliper immediately before and 2, 4, and 6 h after injection of Aerosil. KET-loaded ME showed particle size around 20 nm, with zeta potential at −16 mV and entrapment efficiency at 70%. Moreover, KET was converted to the amorphous state when loaded in the formulation and it was shown that the drug was slowly released from the ME. Finally, the in vivo biological activity was similar to that of the commercial gel, but ME better controlled edema at 4 h. These results demonstrated that the ME formulation is an alternative strategy for improving KET skin permeation for anti-inflammatory effect. Furthermore, our findings are promising considering that the developed ME was loaded with only 1% KET, and the formulation was able to keep a similar release profile and in vivo effect compared to the commercial gel with 2.5% KET. Therefore, the KET-loaded developed herein ME is likely to have a decreased side effect compared with that of the commercial gel, but both presented the same efficacy.

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Acknowledgements

The authors thank Henrique Diniz and José Orestes del Ciampo for technical assistance during performance of the experiments.

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Authors and Affiliations

  1. Faculdades Integradas Padre Albino–FIPA, Rua dos Estudantes, 255, Catanduva, São Paulo, 15809-144, Brazil

    Ana Luisa Murbach Aliberti, Alemer Cortat de Queiroz & Wanessa Silva Garcia Medina

  2. Faculdade de Ciências Farmacêuticas de Ribeirão Preto, Universidade de São Paulo, Av. do Café, s/n, Ribeirão Preto, São Paulo, 14040-903, Brazil

    Fabíola Silva Garcia Praça, Josimar O. Eloy & Maria Vitória Lopes Badra Bentley

Authors
  1. Ana Luisa Murbach Aliberti
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  2. Alemer Cortat de Queiroz
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  3. Fabíola Silva Garcia Praça
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  4. Josimar O. Eloy
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  5. Maria Vitória Lopes Badra Bentley
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  6. Wanessa Silva Garcia Medina
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Corresponding author

Correspondence to Wanessa Silva Garcia Medina.

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All the experimental procedures were done following the guidelines of the Institutional Animals Ethics Committee (IEAC) and the protocol of the animal study was approved by the Faculdades Integradas Padre Albino animal committee on care and handling animals (Authorization number 15.11.27-06).

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Aliberti, A.L.M., de Queiroz, A.C., Praça, F.S.G. et al. Ketoprofen Microemulsion for Improved Skin Delivery and In Vivo Anti-inflammatory Effect. AAPS PharmSciTech 18, 2783–2791 (2017). https://doi.org/10.1208/s12249-017-0749-6

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  • DOI: https://doi.org/10.1208/s12249-017-0749-6

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