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Nanoemulgel, an Innovative Carrier for Diflunisal Topical Delivery with Profound Anti-Inflammatory Effect: in vitro and in vivo Evaluation

Authors Bashir M, Ahmad J, Asif M, Khan SUD, Irfan M, Y Ibrahim A, Asghar S, Khan IU, Iqbal MS, Haseeb A, Khalid SH, AS Abourehab M

Received 2 December 2020

Accepted for publication 28 January 2021

Published 22 February 2021 Volume 2021:16 Pages 1457—1472


Checked for plagiarism Yes

Review by Single anonymous peer review

Peer reviewer comments 2

Editor who approved publication: Prof. Dr. Thomas J. Webster

Mehreen Bashir,1 Junaid Ahmad,1 Muhammad Asif,2 Salah-Ud-Din Khan,3 Muhammad Irfan,1 Asim Y Ibrahim,4 Sajid Asghar,1 Ikram Ullah Khan,1 Muhammad Shahid Iqbal,5 Abdul Haseeb,6 Syed Haroon Khalid,1 Mohammed AS Abourehab7,8

1Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan; 2Department of Pharmacology, Faculty of Pharmacy, The Islamia University of Bahawalpur, Bahawalpur, Pakistan; 3Department of Biochemistry, College of Medicine, Imam Mohammad Ibn Saud Islamic University, Riyadh, Saudi Arabia; 4Faculty of Pharmacy, Omdurman Islamic University, Omdurman, Sudan; 5Department of Clinical Pharmacy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Alkharj, Saudi Arabia; 6Department of Clinical Pharmacy, College of Pharmacy, Umm Al-Qura University, Makkah, 21955, Saudi Arabia; 7Department of Pharmaceutics, Faculty of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia; 8Department of Pharmaceutics and Industrial Pharmacy, Faculty of Pharmacy, Minia University, Minia, Egypt

Correspondence: Syed Haroon Khalid
Department of Pharmaceutics, Faculty of Pharmaceutical Sciences, Government College University, Faisalabad, 38000, Pakistan
Tel +92-3166752223

Purpose: Rheumatoid arthritis is an autoimmune disorder that directly affects joints. However, other body organs including heart, eyes, skin, blood vessels and lungs may also be affected. The purpose of this study was to design and evaluate a nanoemulgel formulation of diflunisal (DIF) and solubility enhanced diflunisal (DIF-IC) for enhanced topical anti-inflammatory activity.
Methodology: Nanoemulsion formulations of both DIF and DIF-IC were prepared and incorporated in three different gelling agents, namely carboxymethylcellulose sodium (CMC-Na), sodium alginate (Na-ALG) and xanthan gum (XG). All the formulations were evaluated in term of particle size, pH, conductivity, viscosity, zeta potential and in vitro drug release. The formulation 2 (NE2) of both DIF and DIF-IC which expressed optimum release and satisfactory physicochemical properties was incorporated with gelling agents to produce final nanoemulgel formulations. The optimized nanoemulgel formulation was subjected to three different in vivo anti-inflammatory models including carrageenan-induced paw edema model, histamine-induced paw edema model and formalin-induced paw edema model.
Results: DIF-IC-loaded nanoemulgel formulations yielded significantly enhanced in vitro skin permeation than DIF-loaded nanoemulgel. The nanoemulgel formulation of DIF-IC formulated with XG produced improved in vivo anti-inflammatory activity.
Conclusion: It was recommended that DIF-IC-based nanoemulgel formulation prepared with XG could be a better option for effective topical treatment of inflammatory conditions.

Keywords: diflunisal, nanoemulsion, pseudoternary phase diagram, in vitro skin permeation, anti-inflammatory activity, improved efficacy

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