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Design and optimization of film-forming gel of etoricoxib using research surface methodology

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Abstract

The present investigation is focused on the development of transdermal film-forming gel (FFG) loaded with etoricoxib employing research surface methodology (RSM). Box-Behnken surface design method was used to develop experimental run using different concentrations of etoricoxib, hydroxypropyl methylcellulose (HPMC K100M), and eudragit RL100 as independent variables, and Derringer’s optimization tool was employed to optimize best possible formulation. The dependent variables considered in this study were viscosity and drug permeation at 24 h (Q24, μg/cm2). Anti-inflammatory study was performed on Wistar albino rats for 8 h. Skin irritation studies and accelerated stability studies were performed for validated FFG formulations. Quadratic model was found to be best fit model (p < 0.0001) for both the responses. The influence of HPMC concentration on the viscosity was found to be highest whereas concentration of etoricoxib was maximum for Q24. The optimum composition of the FFG was observed to be 4% of etoricoxib, 1.1246% of HPMC, and 0.4% of eudragit. Above composition resulted in viscosity of 1549.5 mPa.s and maximum Q24 of 4639.11 μg/cm2 with desirability 0.918. The in vivo anti-inflammatory study demonstrated better sustained release effect (for 8 h) of optimized FFG compared to orally administered drug suspension. An average irritation score of 0.555 was observed on Draize scoring system. The validated FFG formulation was found to be stable for the 3 months in accelerated conditions. It can be concluded from the above investigations that the validated FFG formulation of etoricoxib is well tolerated and could provide sustained drug release for 8 h.

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Abbreviations

DSC:

differential scanning calorimeter

HPMC:

hydroxypropyl methylcellulose

FFG:

film-forming gel

DOE:

design of experiments

RSM:

research surface methodology

NSAIDs:

non-steroidal anti-inflammatory drugs

COX-2:

cyclooxygenase-2

HPLC:

high-performance liquid chromatography

CV:

coefficient of variation

SC:

stratum corneum

Q24:

amount of drug permeated per unit area

ANOVA:

analysis of variance

DDW:

double distilled water

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Acknowledgments

The authors are thankful to Dr. Sumanta Mondal, Assistant Professor, GITAM Institute of Pharmacy, GITAM Deemed to be University, Visakhapatnam campus for helping in conducting in vivo study. The authors also grateful to the management of GITAM Deemed to be University, Visakhapatnam, for providing facilities for the smooth conduct of the research work.

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The present investigation is self-funded.

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  1. GITAM Institute of Pharmacy, GITAM (Deemed to be University), Gandhi Nagar Campus, Rushikonda, Visakhapatnam, Andhra Pradesh, 530045, India

    Rabinarayan Parhi & V. V. Nishanth Goli

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The study was designed by Rabinarayan Parhi and performed by V.V. Nishanth Goli. The interpretation and writing of the manuscript was carried out by Rabinarayan Parhi. All the authors have approved the final manuscript.

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Parhi, R., Goli, V.V.N. Design and optimization of film-forming gel of etoricoxib using research surface methodology. Drug Deliv. and Transl. Res. 10, 498–514 (2020). https://doi.org/10.1007/s13346-019-00695-2

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