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INTRODUCTION
Topical corticosteroids are first-line drugs in the therapy of acute exacerbations of atopic dermatitis and contact dermatitis. Betamethasone-17-Valerate (BMV) is the gold standart of these agents and serves as reference in clinical studies for new glucocorticosteroids [1]. Chitosan, a natural poly-(aminosaccharide), is non-toxic and easily bioabsorbable and currently in use for the release of several drugs [2]. The most widely used approach to drug permeation-enhancement across the stratum corneum barrier is the use of chemical penetration enhancers. Enhancers are compounds which can increase the permeability of the stratum corneum by either increasing drug diffusivity and/or by increasing drug partition [3]. The aim of this study was to evaluate the enhancement effect of three different types of enhancers (Oleic acid, D-limonene and 2-pyrrolidone) on the in vitro release of BMV gels. Propylene glycol was chosen as co-enhancer in this study.
0,0035 0,003
Flux of BMV
Enhancers
D-limonene
2-pyrrolidone
Figure 1 Effect of enhancers on the flux of BMV from chitosan gels When all kinetical parameters evaluated together, no significant correlation was established among the enhancers. ER value was found higher than control in all cases. D-limonene provided the best enhancement activity between the enhancers studied (Table 1, Figure 1). By the way, when the amount of drug at the end of six hours was investigated, D-limonene and Oleic acid exhibited higher drug release when compared with 2-pyrrolidone (Table 1). It was reported that propylene glycol has showed synergic effect with many enhancers such as Oleic acid and D-limonene [5]. So, the results of this study could be due to the synergic effect between D-limonene, Oleic acid and propylene glycol. In addition, Dlimonene increased the thermodynamic activity of BMV and the released amount of BMV has been increased. However, 2pyrrolidone showed same drug release and lag time with control formulation (Table 1).
CONCLUSION
On the basis of above observations, it can be concluded that Dlimonene and Oleic acid could be suitable enhancers in the presence of propylene glycol for high molecular weight chitosan gels of BMV.
ACKNOWLEDGEMENTS
The authors are grateful to the Novartis Drug Company for its financial support of this study.
REFERENCES
[1] R. Sivaramakrishnan, C. Nakamura, W. Mehnert, H.C. Korting, K.D. Kramer, M. Schafer-Korting, J. Cont. Rel. 97 493-502 (2004). [2] K.C. Gupta, M.N.V. Ravi Kumar, Biomaterials 21 1115-1119 (2000). [3] P.A. Cornwell, B.W. Barry, J.A. Bouwstra, G.S. Gooris, Int. J. Pharm. 127 9-26 (1996). [4] T. enyiit, .zer, 8th International Conference of the European Chitin Society, 8-11 September, Antalya-Turkey p. 152 (2007) [5] I. Z. Schroeder, P. Franke, U.F. Schaefer, C.M. Lehr, J. Cont. Rel. 118 196-203 (2007).
ERflux=