Formulation and evaluation of ketoprofen loaded chitosan nanogel for pain management: Ex-vivo and In-vivo study
DOI:
https://doi.org/10.30827/ars.v60i2.8563Keywords:
ransdermal delivery, ketoprofen, nanogelAbstract
Purpose: The purpose of this study was to develop and evaluate nanoemulsion-based gel (nanogel) for transdermal delivery of ketoprofen. Among the various excipients tested, oleic acid, tween 80 and ethanol were selected as oil, surfactant, and co-surfactant respectively.
Methods: The nanoemulsions region was identified by constructing pseudo-ternary phase diagrams using aqueous phase titration. The prepared nanoemulsion was subjected to different thermodynamic stability study and the nanoemulsion that passed thermodynamic stability tests were evaluated for viscosity, refractive index, droplet size, transmission electron microscopy, and ex-vivo permeation study using human cadaver skin.
Results: On the basis of evaluation C1 formulation, which consists of 3.09 % wt/wt of the oil phase, 60.54 % wt/wt of Smix and 36.36 % wt/wt of distilled water were selected as an optimized formulation and were converted to nanogel using chitosan as a gelling agent. Nanogel was evaluated for ex-vivo and in vivo study. The nanogel showed a significant increase in the anti-inflammatory activity as compared to conventional gel.
Conclusion: In conclusion, nanogel could be a promising system to improve transdermal delivery of the ketoprofen.
Downloads
References
Suzuki T, Shinoda M, Osanai Y, Isozaki T. Photochemical reaction of 2-(3-benzoylphenyl)propionic acid (ketoprofen) with basic amino acids and dipeptides. J Phys Chem B. 2013;117(33):9662–8.
Miller MA, Pisani E. The cost of unsafe injections. Vol. 77, Bulletin of the World Health Organization. 1999. p. 808–11.
Callaghan TM, Wilhelm KP. A review of ageing and an examination of clinical methods in the assessment of ageing skin. Part 2: Clinical perspectives and clinical methods in the evaluation of ageing skin. Vol. 30, International Journal of Cosmetic Science. 2008. p. 323–32.
Shakeel F, Baboota S, Ahuja A, Ali J, Aqil M, Shafiq S. Nanoemulsions as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech. 2007;8(4):191–9.
Singh B, Singh R, Bandyopadhyay S, Kapil R, Garg B. Optimized nanoemulsifying systems with enhanced bioavailability of carvedilol. Colloids Surfaces B Biointerfaces. 2013;101:465–74.
Zhao JH, Ji L, Wang H, Chen ZQ, Zhang YT, Liu Y, et al. Microemulsion-based novel transdermal delivery system of tetramethylpyrazine: preparation and evaluation in vitro and in vivo. Int J Nanomedicine. 2011;6:1611–9.
Swarbrick J, Boylan JC. Encyclopedia of pharmaceutical technology. Vol. 20, Pharmaceutical Technology. 1996. 23-24 p.
Lawrence MJ, Rees GD. Microemulsion-based media as novel drug delivery systems. Vol. 64, Advanced Drug Delivery Reviews. 2012. p. 175–93.
Muxika A, Etxabide A, Uranga J, Guerrero P, Caba K De. International Journal of Biological Macromolecules Chitosan as a bioactive polymer : Processing , properties and applications. Int J Biol Macromol [Internet]. 2017;105:1358–68. Doi: 10.1016/j.ijbiomac.2017.07.087
S. A, S. I. Chitosan & its derivatives: A review in recent innovations. Int J Pharm Sci Res. 2015;6(1):14–30.
Azuma K, Izumi R, Osaki T, Ifuku S, Morimoto M, Saimoto H, et al. Chitin, Chitosan, and Its Derivatives for Wound Healing: Old and New Materials. J Funct Biomater. 2015;6(1):104–42.
Okamoto Y, Kawakami K, Miyatake K, Morimoto M, Shigemasa Y, Minami S. Analgesic effects of chitin and chitosan. Carbohydr Polym. 2002;49(3):249–52.
Pathan IB, Mallikarjuna Setty C. Nanoemulsion system for transdermal delivery of tamoxifen citrate: Design, Characterization, effect of penetration enhancers and in vivo studies. Dig J Nanomater Biostructures. 2012;7(4):1373–87.
Shafaat K, Kumar B, Das SK, Ul Hasan R, Prajapati SK. Novel nanoemulsion as vehicles for transdermal delivery of Clozapine: In vitro and in vivo studies. Int J Pharm Pharm Sci. 2013;5(SUPPL 3):126–34.
Soliman SM, Abdel Malak NS, El-Gazayerly ON, Abdel Rehim a a. Formulation of microemulsion gel systems for transdermal delivery of celecoxib: In vitro permeation, anti-inflammatory activity and skin irritation tests. Drug Discov Ther [Internet]. 2010;4(6):459–71.
Moreno MA, Ballesteros MP, Frutos P. Lecithin-based oil-in-water microemulsions for parenteral use: Pseudoternary phase diagrams, characterization and toxicity studies. J Pharm Sci. 2003;92(7):1428–37.
Shafiq S, Shakeel F, Talegaonkar S, Ahmad FJ, Khar RK, Ali M. Development and bioavailability assessment of ramipril nanoemulsion formulation. Eur J Pharm Biopharm. 2007;66(2):227–43.
Bhatt P, Madhav S. A detailed review on nanoemulsion drug delivery system. Int J Pharm Sci Res. 2011;43(2):2292–8.
Liu CH, Yu SY. Cationic nanoemulsions as non-viral vectors for plasmid DNA delivery. Colloids Surfaces B Biointerfaces. 2010;79(2):509–15.
Pathan IB, Munde SJ, Shelke S, Ambekar W, Mallikarjuna Setty C. Curcumin loaded fish scale collagen-HPMC nanogel for wound healing application: Ex-vivo and In-vivo evaluation. Int J Polym Mater Polym Biomater. 2018;
Fang JY, Sung KC, Lin HH, Fang CL. Transdermal iontophoretic delivery of diclofenac sodium from various polymer formulations: in vitro and in vivo studies. Int J Pharm. 1999;178(1):83–92.
Shakeel F. Criterion for excipients screening in the development of nanoemulsion formulation of three anti-inflammatory drugs. Pharm Dev Technol [Internet]. 2010;15(2):131–8.
Pathan IB, Jaware BP, Shelke S, Ambekar W. Curcumin loaded ethosomes for transdermal application: Formulation, optimization, in-vitro and in-vivo study. J Drug Deliv Sci Technol. 2018;44.
Pouton CW, Porter CJH. Formulation of lipid-based delivery systems for oral administration: Materials, methods and strategies. Vol. 60, Advanced Drug Delivery Reviews. 2008. p. 625–37.
Silva HD, Cerqueira MA, Vicente AA. Influence of surfactant and processing conditions in the stability of oil-in-water nanoemulsions. J Food Eng. 2015;167:89–98.
Arora P, Mukherjee B. Design, development, physicochemical, and in vitro and in vivo evaluation of transdermal patches containing diclofenac diethylammonium salt. J Pharm Sci. 2002;91(9):2076–89.
Tadros TF. Emulsion Formation, Stability, and Rheology. In: Emulsion Formation and Stability. 2013. p. 1–75.
Published
How to Cite
Issue
Section
License
Copyright (c) 2019 Inayat Bashir Pathan, Rashmi Dwivedi, Wahid Ambekar
![Creative Commons License](http://i.creativecommons.org/l/by-nc-sa/4.0/88x31.png)
This work is licensed under a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International License.
The articles, which are published in this journal, are subject to the following terms in relation to the rights of patrimonial or exploitation:
- The authors will keep their copyright and guarantee to the journal the right of first publication of their work, which will be distributed with a Creative Commons BY-NC-SA 4.0 license that allows third parties to reuse the work whenever its author, quote the original source and do not make commercial use of it.
b. The authors may adopt other non-exclusive licensing agreements for the distribution of the published version of the work (e.g., deposit it in an institutional telematic file or publish it in a monographic volume) provided that the original source of its publication is indicated.
c. Authors are allowed and advised to disseminate their work through the Internet (e.g. in institutional repositories or on their website) before and during the submission process, which can produce interesting exchanges and increase citations of the published work. (See The effect of open access).