Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib

Baboota, Sanjula; Shakeel, Faiyaz; Ahuja, Alka; Ali, Javed; Shafiq, Sheikh

doi:10.2478/v10007-007-0025-5

Abstract

The aim of the present study was to investigate the potential of nanoemulsion formulations for transdermal delivery of celecoxib (CXB). The in vitro skin permeation profile of optimized formulations was compared with CXB gel and nanoemulsion gel. Significant increase in the steady state flux (J_ss), permeability coefficient (K_p) and enhancement ratio (E_r) was observed in nanoemulsion formulations T1 and T2 (p < 0.05). The highest value of these permeability parameters was obtained in formulation T2, which consisted of 2% (m/m) of CXB, 10% (m/m) of oil phase (Sefsol 218 and Triacetin), 50% (m/m) of surfactant mixture (Tween-80 and Transcutol-P) and 40% (m/m) water. The anti-inflammatory effects of formulation T2 showed a significant increase (p < 0.05) in inhibition after 24 h compared to CXB gel and nanoemulsion gel on carrageenan-induced paw edema in rats. These results suggested that nanoemulsions are potential vehicles for improved transdermal delivery of CXB.

References

E. Escibano, A. C. Calpena, J. Queralt, R. Obach and J. Domenech, Assessment of diclofenac permeation with different formulations: anti-inflammatory study of a selected formula, Eur. J. Pharm. Sci.19 (2003) 203--210; DOI: 10.1016/S0928-0987(03)00103-9.10.1016/S0928-0987(03)00103-9
Search in Google Scholar
Gaurel, A. M. Martel and J. Castaner, Celecoxib, anti-inflammatory, cyclo-oxygenase-2 inhibitor, Drug Future22 (1997) 711--714.
Search in Google Scholar
K. A. Walters, Penetration Enhancers and their Use in Transdermal Therapeutic Systems, in Transdermal Drug Delivery: Developmental Issues and Research Initiatives (Eds. J. Hadgraft and R. H. Guy), Marcel Dekker, New York 1989, pp. 197--246.
Search in Google Scholar
D. W. Osborne, A. J. Ward and K. J. Neil, Microemulsions as topical delivery vehicles: in-vitro transdermal studies of a model hydrophilic drug, J. Pharm. Phamacol.43 (1991) 450--454.
Search in Google Scholar
M. Trotta, F. Pattarino and M. R. Gasco, Influence of counter ions on the skin permeation of methotrexate from water-oil microemulsions, Pharm. Acta. Helv.71 (1996) 135--140; DOI: 10.1016/0031-6865(96)00003-9.10.1016/0031-6865(96)00003-9
Search in Google Scholar
S. Shafiq, S. Faiyaz, T. Sushma, J. A. Farhan, R. K. Khar and M. Ali, Design and development of ramipril nanoemulsion formulation: In vitro and in vivo assessment, J. Biomed. Nanotechnol.3 (2007) 28--44; DOI: 10.1166/jbn.2007.008.10.1166/jbn.2007.008
Search in Google Scholar
S. Shafiq, S. Faiyaz, T. Sushma, J. A. Farhan, R. K. Khar and M. Ali, Development and bioavailability assessment of ramipril nanoemulsion formulation, Eur. J. Pharm. Biopharm.66 (2007) 227--243; DOI: org/10.1016/j.ejpb.2006.10.014.
Search in Google Scholar
M. B. Delgado-Charro, G. Iglesias-Vilas, J. Blanco-Mendez, M. J. Lopez-Quintela, M. A. Marty and J. P. Guy, Delivery of a hydrophilic solute through the skin from novel microemulsion systems, Eur. J. Pharm. Biopharm.43 (1997) 37--42; DOI: 10.1016/S0939-6411(96)00016-1.10.1016/S0939-6411(96)00016-1
Search in Google Scholar
M. Kreilgaard, E. J. Pedersen and J. W. Jaroszewski, NMR characterization and transdermal drug delivery potentials of microemulsion systems, J. Control. Rel.69 (2000) 421--433; DOI: 10.1016/S0168-3659(00)00325-4.10.1016/S0168-3659(00)00325-4
Search in Google Scholar
P. J. Lee, R. Langer and V. P. Shastri, Novel microemulsion enhancer formulation for simultaneous transdermal delivery of hydrophilic and hydrophobic drugs, Pharm. Res.20 (2003) 264--269; DOI: 10.1023/A:1022283423116.10.1023/A:1022283423116
Search in Google Scholar
M. Kreilgaard, Dermal pharmacokinetics of microemulsion formulations determined by in-vitro microdialysis, Pharm. Res.18 (2001) 367--373; DOI: 10.1023/A:1011067300397.10.1023/A:1011067300397
Search in Google Scholar
M. Kreilgaard, M. J. B. Kemme, J. Burggraaf, R. C. Schoemaker and A. F. Cohen, Influence of a microemulsion vehicle on cutaneous bioequivalence of a lipophilic model drug assessed by microdialysis and pharmacodynamics, Pharm. Res.18 (2001) 593--599; DOI: 10.1023/A:1011068907416.10.1023/A:1011068907416
Search in Google Scholar
M. R. Gasco, M. Gallarate and F. Pattarino, In-vitro permeation of zelaic acid from viscosized microemulsions, Int. J. Pharm.69 (1991) 193--196; DOI: 10.1016/0378-5173(91)90361-Q.10.1016/0378-5173(91)90361-Q
Search in Google Scholar
K. Kriwet and C. C. Muller-Goymann, Diclofenac release from phospholipids drug systems and permeation through excised human stratum corneum, Int. J. Pharm.125 (1995) 231--242; DOI: 10.1016/0378-5173(95)00130-B.10.1016/0378-5173(95)00130-B
Search in Google Scholar
S. Baboota, F. Shakeel, A. Ahuja, J. Ali, S. Shafiq and S. Ahmed, Development and validation of stability indicating HPLC method for analysis of Celecoxib in bulk drug and microemulsion formulations, Acta Chromat. (in press).
Search in Google Scholar
N. J. Van Abbe, P. Nicholas and E. Boon, Exaggerated exposure in topical irritancy and sensitization testing, J. Soc. Cosmet. Chem.26 (1975) 173--187.
Search in Google Scholar
C. A. Winter, Anti-inflammatory testing methods: Comparative evaluation of indomethacin and other agents, NSAID, 82 (1965) 190--202.
Search in Google Scholar
M. N. Gosh, Fundamentals of Experimental Pharmacology, 3^rd ed., Hilton and Co., Kolkata 2005, p. 192.
Search in Google Scholar
D. Q. M. Craig, S. A. Barker, D. Banning and S. W. Booth, An investigation into the mechanisms of self-emulsification using particle size analysis and low frequency dielectric spectroscopy, Int. J. Pharm.114 (1995) 103--110; DOI: 10.1016/0378-5173(94)00222-Q.10.1016/0378-5173(94)00222-Q
Search in Google Scholar
K. Kawakami, T. Yoshikawa, Y. Moroto, E. Kanaoka, K. Takahashi, Y. Nishihara and K. Masuda, Microemulsion formulation for enhanced absorption of poorly soluble drugs I. Prescription design, J. Control. Rel.81 (2002) 65--74; DOI: 10.1016/S0168-3659(02)00049-4.10.1016/S0168-3659(02)00049-4
Search in Google Scholar
M. J. Lawrence and G. D. Rees, Microemulsion-based media as novel drug delivery systems, Adv. Drug Deliv. Rev.45 (2000) 89--121; DOI: 10.1016/S0169-409X(00)00103-4.10.1016/S0169-409X(00)00103-4
Search in Google Scholar
W. Warisnoicharoen, A. B. Lansley and M. J. Lawrence, Light scattering investigations on dilute non-ionic oil-in-water microemulsions, AAPS PharmSci.2 (2000) article 12; DOI: 10.1208/ps020212.10.1208/ps020212275102611741228
Search in Google Scholar
L. Ping, A. Ghosh, R. F. Wagner, S. Krill, Y. M. Joshi and A. T. M. Serajuddin, Effect of combined use of nonionic surfactant on formation of oil-in-water microemulsions, Int. J. Pharm.288 (2005) 27--34; DOI: 10.1016/jijpharm.2004.08.024.
Search in Google Scholar
K. Shinoda and H. Kunieda, Phase Properties of Emulsions: PIT and HLB, in Encyclopedia of Emulsion Technolog (Eds. K. Shinoda and H. H. Kunieda), Marcel Dekker, New York 1983, pp. 337--367.
Search in Google Scholar
N. J. Kale and A. V. Allen, Studies on microemulsions using Brij-96 as surfactant and glycerin, ethylene glycol and propylene glycol as cosurfactants, Int. J. Pharm.57 (1998) 87--93; DOI: 10. 1016/0378-5173(89)90296-2.
Search in Google Scholar
D. Thacrodi and R. K. Panduranga, Transdermal absorption of nifedipine from microemulsions of lipophilic skin penetration enhancers, Int. J. Pharm.111 (1994) 235--240; DOI: 10.1016/0378--5173(94)90346-8.
Search in Google Scholar

Design, development and evaluation of novel nanoemulsion formulations for transdermal potential of celecoxib

Abstract

Paradigm

My account