FORMULATION AND OPTIMIZATION OF CELECOXIB NANOEMULGEL
Objective: The main objective of this experiment was to prepare and optimized celecoxib nanoemulgel. This formulation can be used for acuterheumatoid arthritis patients.
Methods: Celecoxib is a poorly water soluble drug. We prepared celecoxib nanoemulgel to improve intrinsic solubility of celecoxib and enhancedeeper permeation throughout the skin. After several screening, the combination of acetonitrile, triacetin, campul 908P was considered for oil phase;acconon MC8-2EP as surfactant, and capmul MCM C-10 as a co-surfactant accordingly. As per Box-Behnken surface design model, optimization wasdone for all the 13 formulations.
Results: Based on pseudo ternary plot, it was found that 4:1 Smix ratio was optimum and possessed maximum drug solubility. Further, screeningshown, 0.25-0.75% carbopol-940 can be a stable candidate for hydrogel preparation. Prepared nanoemulsions and hydrogels were admixed to preparenanoemulgel. Based on overlay plot, EG14* formulation was consider as optimum one, and various evaluation parameters were performed along withother formulations. Using Franz diffusion cell, in-vitro diffusion studies was performed. Almost all the formulations produces good qualitative drugrelease profile. The EG14* shown 95.50% drug release after 12th hrs with standard Higuchi plot (R2 value 0.9989). The optimum viscosity was foundto be 521Â±0.81 mPas at 100 rpm. The appearance of the formulations was milky, yellowish white with expectable pH ranged from 5.8 to 6.7. Theoptimized formulation has good spreadability coefficient, good ex-vivo diffusion enhancement factor (3.03) as compare to marketed gel. Mostly, ourformulations have less skin irritation and higher anti-inflammatory activity (92.56% of inhibition of paw edema for EG14*).
Conclusion: From the thermodynamic studies, it was confirmed that EG14* maintained excellent stability profile in various heating-cooling cycle,centrifugation, and freeze-thaw cycle condition. Hence, it can be conclude that, our formulation, can be consider for pilot scale up.
2. National Institute of Arthritis and Musculoskeletal and Skin Diseases (NIAMS). Handout on Health: Rheumatoid Arthritis; 2009. Available from: http://www.niams.nih.gov/Health_Info/Rheumatic_Disease/ default.asp. [Last accessed on 2012 July 18].
3. Lipsky PE. Rheumatoid arthritis. In: Fauci AS, Kasper DL, Longo DL, Hauser SL, Jameson J, Loscalzo J, et al., editors. Harrisonâ€™s Principles of Internal Medicine. 17th ed. New York, NY: McGraw-Hill; 2008. p. 2083-92.
4. American College of Rheumatology Subcommittee on Rheumatoid Arthritis Guidelines. Guidelines for the management of rheumatoid arthritis 2002 update. Arthritis Rheum 2002;46(2):328-46.
5. American College of Rheumatology. What is a rheumatologist? Atlanta, GA: American College of Rheumatology; 2010. Available from: http:// www.rheumatology.org/practice/clinical/patients/rheumatologist. [Last accessed on 2012 May 07].
6. Bolten WW. Scientific rationale for specific inhibition of COX-2. J Rheumatol Suppl 1998;51:2-7.
7. Cryer B, Feldman M. Cyclooxygenase-1 and cyclooxygenase-2 selectivity of widely used nonsteroidal anti-inflammatory drugs. Am J Med 1998;104(5):413-21.
8. Micromedex. Celecoxib - Monograph UBAT-184. Drug Information- Disc B. Vol. 112; 2002. Available from: http://www.bpfk.gov.my/ pdfworddownload/publication/184.pdf.
9. Chen H, Chang X, Du D, Li J, Xu H, Yang X. Microemulsion-based hydrogel formulation of ibuprofen for topical delivery. Int J Pharm 2006;315(1-2):52-8.
10. Zhu W, Guo C, Yu A, Gao Y, Cao F, Zhai G. Microemulsion-based hydrogel formulation of penciclovir for topical delivery. Int J Pharm 2009;378(1-2):152-8.
11. Asija R. Emulgel: A novel approach to topical drug delivery. J Biomed Pharm Res 2013;2:91-4.
12. Panwar A, Upadhyay N, Bairagi M, Gujar S, Darwhekar GN, Jain DK, et al. Emulgel: A review. Asian J Pharm Life Sci 2011;1:333-43.
13. Gannu R, Palem CR, Yamsani VV, Yamsani SK, Yamsani MR. Enhanced bioavailability of lacidipine via microemulsion based transdermal gels: Formulation optimization, ex vivo and in vivo characterization. Int J Pharm 2010;388(1-2):231-41.
14. Elmarzugi NA, Keleb EI, Mohamed AT, Issa YS, Hamza AM, Dlim MM, et al. The relation between sunscreen and skin pathchanges mini review. Int J Pharm Sci Invent 2013;2:43-52.
15. Shakeel F, Baboota S, Ahuja A, Ali J, Aqil M, Shafiq S. Nanoemulsion as vehicles for transdermal delivery of aceclofenac. AAPS PharmSciTech 2007;8:1-9.
16. Shafiq-un-Nabi S, Shakeel F, Talegaonkar S, Ali J, Baboota S, Ahuja A, et al. Formulation development and optimization using nanoemulsion technique: A technical note. AAPS PharmSciTech 2007;8(2):Article 28.
17. Sisinthy SP, Rao NK, Sarah CY. Design, optimization and in vitro characterization of self-nano emulsifying drug delivery system of olmesartanmedoxomil. Int J Pharm Pharm Sci 2017;9(1):94-101.
18. Date AA, Nagarsenker MS. Design and evaluation of self-nanoemulsifying drug delivery systems (SNEDDS) for cefpodoxime proxetil. Int J Pharm 2007;329(1-2):166-72.
19. Aggarwal RA, Kumar SL, Kaur KD. Nanoemulsion based hydrogel for enhanced transdermal delivery of ketoprofen. Adv Pharm 2014;1:3-15.
20. Ngawhirunpat T, Worachun N, Panasopit PO, Rojanarata T, Panomsuk S. Cremophor RH40-PEG400 micro emulsions as transdermal drug delivery carrier for ketopofen. Pharm Dev Technol 2013;18(4):798-803.
21. Karade PG, Rohit RS, Chougale DD, Bhise SB. Formulation and evaluation of celecoxib gel. J Drug Deliv Ther 2012;2(1):132-5.
22. de Graaff AM, Li GL, van Aelst AC, Bouwstra JA. Combined chemical and electrical enhancement modulates stratum corneum structure. J Control Release 2003;90(1):49-58.
23. Desai KG. Enhanced skin permeation of rofecoxib using topical microemulsion gel. Drug Dev Res 2004;63(1):33-40.
24. Preeti GK, Rohit RS, Chougule DD, Bhise SB. Formulation and evaluation of celecoxib gel. J Drug Deliv Ther 2012;2(3):132-5.
25. Shakeel F, Ramadan W, Gargum HM, Singh R. Preparation and in vivo evaluation of indomethacin loaded true nanoemulsions. Sci Pharm 2010;78(1):47-56.
26. Rao KM, Prakash KG, Badarinath AV, Madhusudhanachetty C, Alagusundaram M. Preparation and evaluation of flurbiprofen gel; mucilage of Cocculus hirsutus leaf powder as gel base. Int J Pharm Tech Res 2010;2:1578-83.
27. Shah S, Bhadra S. Mucoadhesive in-situ gel for transmucosal delivery of celecoxib. Int J Pharm Pharm Sci 2014;6(10):221-7.
The publication is licensed under CC By and is open access. Copyright is with author and allowed to retain publishing rights without restrictions.