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Formulation Optimization and Ex Vivo and In Vivo Evaluation of Celecoxib Microemulsion-Based Gel for Transdermal Delivery

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Abstract

Celecoxib (CXB) is a poorly aqueous solubility sulfonamide non-steroidal anti-inflammatory drug (NSAID). Hence, the formulation of CXB was selected for solubilization and bioavailability. To find out suitable formulation for microemulsion, the solubility of CXB in triacetin (oil phase), Tween 80 (surfactant), and Transcutol-P (co-surfactant) was screened respectively and optimized by using orthogonal experimental design. The Km value and concentration of oil, Smix, and water were confirmed by pseudo-ternary phase diagram studies and central composite design. One percent carbopol 934 was added to form CXB microemulsion-based gel. The final formulation was evaluated for its appearance, pH, viscosity, stability, drug content determination, globule size, and zeta potential. Its ex vivo drug permeation and the in vivo pharmacokinetic was investigated. Further research was performed to ensure the safety and validity by skin irritation study and in vivo anti-inflammatory activity study. Ex vivo permeation study in mice was designed to compare permeation and transdermal ability between microemulsion formulation and conventional gel. The results revealed that optimized microemulsion-based gel gained higher permeation based on smaller globule size and high drug loading of microemulsion. Transdermal ability was also greatly improved. Bioavailability was compared to market Celebrex® by the in vivo pharmacokinetic study in rabbits. The results indicated that CXB microemulsion-based gel had better bioavailability than Celebrex®.

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Acknowledgements

The authors are thankful to Jiangsu ChiaTai QingJiang Pharmaceutical Co. Ltd., for generously providing the gift sample of CXB. The authors also thank the Jiangsu Institute of Pharmacy, School of Pharmaceutical Sciences, Nanjing Tech University, for providing the necessary facilities.

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Authors and Affiliations

  1. School of Pharmaceutical Sciences, Nanjing University of Technology, 5th Mofan Road, Nanjing, 210009, China

    Mengyuan Cao, Lili Ren & Guoguang Chen

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  1. Mengyuan Cao
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  2. Lili Ren
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  3. Guoguang Chen
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Correspondence to Guoguang Chen.

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The in vivo pharmacokinetic study of CXB microemulsion-based gel was implemented on the basis of the “Principles of Laboratory Animal Care” and was permitted by the Nanjing Medical University Institutional Animal.

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Cao, M., Ren, L. & Chen, G. Formulation Optimization and Ex Vivo and In Vivo Evaluation of Celecoxib Microemulsion-Based Gel for Transdermal Delivery. AAPS PharmSciTech 18, 1960–1971 (2017). https://doi.org/10.1208/s12249-016-0667-z

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  • DOI: https://doi.org/10.1208/s12249-016-0667-z

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