Novel Microemulsion Enhancer Formulation for Simultaneous Transdermal Delivery of Hydrophilic and Hydrophobic Drugs
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Purpose. Microemulsion (ME) systems allow for the microscopic co-incorporation of aqueous and organic phase liquids. In this study, the phase diagrams of four novel ME systems were characterized.
Methods. Water and IPM composed the aqueous and organic phases respectively, whereas Tween 80 served as a nonionic surfactant. Transdermal enhancers such as n-methyl pyrrolidone (NMP) and oleyl alcohol were incorporated into all systems without disruption of the stable emulsion.
Results. A comparison of a W/O ME with an O/W ME of the same system for lidocaine delivery indicated that the O/W ME provides significantly greater flux (p < 0.025). The water phase was found to be a crucial component for flux of hydrophobic drugs (lidocaine free base, estradiol) as well as hydrophilic drugs (lidocaine HCl, diltiazem HCl). Furthermore, the simultaneous delivery of both a hydrophilic drug and a hydrophobic drug from the ME system is indistinguishable from either drug alone. Enhancement of drug permeability from the O/W ME system was 17-fold for lidocaine free base, 30-fold for lidocaine HCl, 58-fold for estradiol, and 520-fold for diltiazem HCl.
Conclusions. The novel microemulsion systems in this study potentially offers many beneficial characteristics for transdermal drug delivery.
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- 1.R. P. Bagwe, J. R. Kanicky, B. J. Palla, P. K. Patanjali, and D. O. Shah. Improved drug delivery using microemulsions: rationale, recent progress, and new horizons. Crit. Rev. Ther. Drug Carrier Syst. 18:77-140 (2001).Google Scholar
- 2.M. Trotta, M. R. Gasco, and S. Morel. Release of drugs from oil-water microemulsions. J. Control. Release 10:237-243 (1989).Google Scholar
- 3.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. 71:135-140 (1996).Google Scholar
- 4.D. W. Osborne, A. J. Ward, and K. J. O'Neill. Microemulsions as topical drug delivery vehicles: in-vitro transdermal studies of a model hydrophilic drug. J. Pharm. Pharmacol. 43:451-454 (1991).Google Scholar
- 5.H-O. Ho, C-C. Hsiao, and M-T. Sheu. Preparation of microemulsions using polyglycerol fatty acid esters as surfactant for the delivery of protein drugs. J. Pharm. Sci. 85:138-143 (1996).Google Scholar
- 6.J. Guo, Q. Ping, G. Sun, and C. Jiao. Lecithin vesicular carriers for transdermal delivery of cyclosporin A. Int. J. Pharm. 194:201-207 (2000).Google Scholar
- 7.Q. Zhang, G. Yie, Y. Li, Q. Yang, and T. Nagau. Studies on the cyclosporin A loaded stearic acid nanoparticles. Int. J. Pharm. 200:153-159 (2000).Google Scholar
- 8.M. E. Baca-Estrada, M. Foldvari, C. Ewen, I. Badea, and L. A. Babiuk. Effects of IL-12 on immune responses induced by transcutaneous immunization with antigens formulated in a novel lipid-based biphasic delivery system. Vaccine 18:1847-1854 (2000).Google Scholar
- 9.K. A. Walters, P. H. Dugard, and A. T. Florence. Non-ionic surfactants and gastric mucosal transport of paraquat. J. Pharm. Pharmacol. 33:207-213 (1981).Google Scholar
- 10.P. P. Sarpotdar and J. L. Zatz. Evaluation of penetration enhancement of lidocaine by nonionic surfactants through hairless mouse skin in vitro. J. Pharm. Sci. 75:176-181 (1986).Google Scholar
- 11.M. L. Francoeur, G. M. Golden, and R. O. Potts. Oleic acid: its effects on stratum corneum in relation to (trans)dermal drug delivery. Pharm. Res. 7:621-627 (1990).Google Scholar
- 12.D. D. Kim and Y. W. Chien. Transdermal delivery of dideoxynucleoside-type anti-HIV drugs: the effect of vehicle and enhancer on skin permeation. J. Pharm. Sci. 85:214-219 (1996).Google Scholar
- 13.H. Sasaki, M. Kojima, J. Nakamura, and J. Shibasaki. Enhancing effect of combining two pyrrolidone vehicles on transdermal drug delivery. J. Pharm. Pharmacol. 42:196-199 (1990).Google Scholar
- 14.C. A. Phillips and B. B. Michniak. Transdermal delivery of drugs with differing lipophilicities using azone analogs as dermal penetration enhancers. J. Pharm. Sci. 84:1427-1433 (1995).Google Scholar
- 15.K. Yoneto, S. K. Li, A. H. Ghanem, D. J. Crommelin, and W. I. Higuchi. A mechanistic study of the effects of the 1-alkyl-2-pyrrolidones on bilayer permeability of stratum corneum lipid liposomes: a comparison with hairless mouse skin studies. J. Pharm. Sci. 84:853-860 (1995).Google Scholar
- 16.M. E. Johnson, S. Mitragotri, A. Patel, D. Blankschtein, and R. Langer. Synergistic effects of chemical enhancers and therapeutic ultrasound on transdermal drug delivery. J. Pharm. Sci. 85:670-679 (1996).Google Scholar
- 17.M. E. Johnson, D. Blankschtein, and R. Langer. Permeation of steroids through human skin. J. Pharm. Sci. 84:1144-1146 (1995).Google Scholar
- 18.Y. W. Chien, T. Y. Chien, R. E. Bagdon, Y. C. Huang, and R. H. Bierman. Transdermal dual-controlled delivery of contraceptive drugs: formulation development, in vitro and in vivo evaluations, and clinical performance. Pharm. Res. 12:1000-1010 (1989).Google Scholar
- 19.M. S. Powers, L. Schenkel, P. E. Darley, W. R. Good, J. C. Balestra, and V. A. Place. Pharmacokinetics and pharmacodynamics of transdermal dosage forms of 17 beta-estradiol: comparison with conventional oral estrogens used for hormone replacement. Am. J. Obstet. Gynecol. 152:1099-1106 (1985).Google Scholar
- 20.P. D. Huibers. Surfactant Self-Assembly, Kinetics and Thermodynamics of Micellar and Microemulsion Systems. Ph.D. Thesis, University of Florida, 1996.Google Scholar
- 21.S. Mitragotri, M. E. Johnson, D. Blankschtein, and R. Langer. An analysis of the size selectivity of solute partitioning, diffusion, and permeation across lipid bilayers. Biophys. J. 77:1268-1283 (1999).Google Scholar
- 22.S. R. Gorukanti, L. Li, and K. H. Kim. Transdermal delivery of antiparkinsonian agent, benztropine. Int. J. Pharm. 192:159-172 (1999).Google Scholar
- 23.S. D. Roy, E. Roos, and K. Sharma. Transdermal delivery of buprenorphine through cadaver skin. J. Pharm. Sci. 83:126-130 (1994).Google Scholar
- 24.K. D. Peck, A. H. Ghanem, and W. I. Higuchi. The effect of temperature upon the permeation of polar and ionic solutes through human epidermal membranes. J. Pharm. Sci. 84:975-982 (1995).Google Scholar
- 25.Physicians Desk Reference 56th Edition. Medical Economics Co. Montvale, New Jersey, p 1016(2002).Google Scholar