Development and Optimization of Proniosomal Gel Containing Etodolac: In-vitro, Ex-vivo and In-vivo Evaluation
DOI:
https://doi.org/10.30827/ars.v62i3.17944Keywords:
Vesicular drug delivery, proniosomal gel, etodolac, non-ionic surfactants, anti- inflammatory studyAbstract
Introduction: Etodolac is used in the treatment of acute pain and inflammation. It has low solubility because of high hydrophobicity and it is reported that upon oral administration shows gastric disturbances. This encourages the development of topical vesicular formulation.
Method: In this work we used coacervation-phase separation method for the development of etodolac loaded vesicular system by using non-ionic surfactants, cholesterol and soya lecithin. Central composite design (rotatble) was used to optimize the concentrations of soy lecithin, surfactant and cholesterol. The prepared formulations were characterized by number of vesicles formed, vesicle size, zeta potential, entrapment efficiency, in-vitro permeation, ex-vivo permeation and anti-inflammatory study.
Results: Etodolac was successfully entrapped in all formulations having efficiency in the range of 74.36% to 90.85%, which was more at 4 °C than room temperature. When hydrated with water; niosome in the range of 54 to 141 (per cubic mm) were spontaneously produced. The results of in-vitro diffusion study revealed that etodolac was released in the range of 71.86 to 97.16% over a period of 24 hrs. The average vesicle size of optimized formulation was found 211.9 nm with PDI of 0.5. The observed responses i.e. % encapsulation efficiency and drug release were 74.12 and 95.08 respectively. The zeta potential was -19.4mV revealed the stability of formulation which was further confirmed by no changes in drug content and drug release after stability studies. The % inhibition in paw volume was 40.52% and 43.61% for test and marketed proniosomal gel.
Conclusion: Proniosomal gel formulation was stable and could enhance skin delivery of etodolac because of excellent permeation capability of vesicular system.
Downloads
References
Heyneman C, Lawless LC, Wall G. Oral versus dermal NSAIDs in rheumatic diseases. Drugs. 2000; 60(3):555–574. doi:10.2165/00003495-200060030-00004.
Okyar A, Ozsoy Y, Gungor S. Novel formulation approaches for dermal and transdermal delivery of non-steroidal anti-inflammatory drugs. En: Lemmey A, editor. Rheumatoid arthritis. Rijeka, Croatia: InTech; 2012. 25-48 p.
Naito Y, Matsuda H, Shimomura K, Kurihara K, Tochigi K, Tomono K. Measurement and correlation of solubilities of the poorly water-soluble pharmaceutical compound etodolac by addition of co-solvents. Fluid Ph Equilibria. 2013; 357(2):43–49. doi: 10.1016/j.fluid.2013.05.025
Tripathi K. Essential of medical pharmacology. 7th ed. New Delhi: Jaypee Brothers Medical Publishers; 192 p.
Rehman K, Zulfakar M. Recent advances in gel technologies for topical and transdermal drug delivery. Drug Dev Ind Pharm. 2014; 40(4):433–440. doi: 10.3109/03639045.2013.828219.
Singla S, Harikumar S, Aggarwal G. Proniosomes for effective topical delivery of clotrimazole: development, characterization and performance evaluation. Asian J Pharm Sci. 2012; 7(4):257–262.
Solanki A, Parikh J, Parikh R. Preparation, ooptimization and characterization of ketoprofen proniosomes for transdermal delivery. Int J Pharm Sci Nanotech. 2009; 2(1):413–420. doi: 10.37285/ijpsn.2009.2.1.4.
Thakur R, Anwer K, Shams M, Ali A, Khar R, Shakeel F, Taha E. Proniosomal transdermal therapeutic system of losartan potassium: development and pharmacokinetic evaluation. J drug Target. 2009; 17(6):442–449. doi: 10.1080/10611860902963039.
Patil H, Hardikar S, Bhosale A. Formulation development and evaluation of proniosomal gel of carvedilol. Int J Pharm Pharm Sci. 2012; 4(1):191–197.
Alsarra I, Bosela A, Ahmed S, Mahrous G. Proniosomes as a drug carrier for transdermal delivery of ketorolac. Eur J Pharm Biopharm. 2005; 59(3):485–490. doi: 10.1016/j.ejpb.2004.09.006.
Guo Y, Pan H, Chen X, Gu Z. Preparation, in vitro and in vivo evaluation of liposomal/niosomal gel delivery systems for clotrimazole. Drug Dev Ind Pharm. 2005; 31(4-5):375–383. doi: 10.1081/ddc-54315.
Shamsheer A, Sabareesh M, Patan K, Saikrishna P, Sudheer B. Formulation and evaluation of lisinopril dihydrate transdermal proniosomal gels. J App Pharm Sci. 2011; 1(8):181–185.
Ueda C, Shah V, Ewing G, Flynn G, Maibach H, Marquis M, Rytting H, Shaw S, Thakker K, Yakobi A. Topical and transdermal drug products. Pharmacopeial Forum, 2009; 35(3):750–764.
Sudhamani T, Priyadarisini N, Radhakrishnan M. Proniosomes: a promising drug carriers. Int J Pharm Tech Res. 2010; 2(2):1446–1454.
Shakeel F, Baboota S, Ahuja A, Ali J, Shafiq S. Skin permeation mechanism and bioavailability enhancement of celecoxib from transdermally applied nanoemulsion. J Nanobiotech. 2008; 6(8):1-11. doi: 10.1186/1477-3155-6-8.
Shakeel F, Baboota S, Ahuja A, Ali J, Shafiq S. Celecoxib nanoemulsion: skin permeation mechanism and bioavailability assessment. J Drug Target. 2008; 16(10):733–740. doi: 10.1080/10611860802473402.
Khullar R, Kumar D, Seth N, Saini S. Formulation and evaluation of mefenamic acid emulgel for topical delivery. Saudi Pharm J. 2012; 20, 63-67. doi: 10.1016/j.jsps.2011.08.001.
Agarwal S, Bakshi V, Vitta P, Raghuram A, Pandey S, Udupa N. Effect of cholesterol content and surfactant HLB on vesicle properties of niosomes. Ind J Pharm Sci. 2004; 66(1):121–123.
Shahiwala A, Misra A. Studies in topical application of niosomally entrapped nimesulide. J Pharm Pharm Sci. 2002; 5(3):220–225.
Shah H, Nair A, Shah J, Bharadia P, Al-Dhubiab B. Proniosomal gel for transdermal delivery of lornoxicam: optimization using factorial design and in vivo evaluation in rats. DARU J Pharm Sci. 2019; 27:59-70. doi: 10.1007/s40199-019-00242-x.
El Zaafarany G, Awad G, Holayel S, Mortada N. Role of edge activators and surface charge in developing ultra deformable vesicles with enhanced skin delivery. Int J Pharm. 2010; 397(1-2):164-172. doi: 10.1016/j.ijpharm.2010.06.034.
Published
How to Cite
Issue
Section
License
Copyright (c) 2021 Ars Pharmaceutica (Internet)
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).
