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Enhanced Transdermal Delivery of Diazepam by Submicron Emulsion (SME) Creams

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Abstract

Diazepam, a lipophilic drug with CNS activity, serves here as a model to investigate the efficacy of SubMicron Emulsion (SME) as a novel transdermal vehicle. Diazepam was formulated in various topical regular creams and SubMicron Emulsion creams of different compositions. The different formulations were applied topically and protection against Pentamethylenetetrazole induced convulsive effects in mice was monitored. The efficacy of Diazepam applied topically in emulsion creams strongly depends on the oil droplet size and to a lesser degree - on the formulation composition and the oil type. Processing medium-chain-triglyceride (MCT) emulsion with a high-pressure homogenizer causes a drastic reduction in the droplet size, thereby significantly increasing the transdermal activity of Diazepam. In this case both the high-pressure homogenization and the presence of lecithin, an efficient dispersant, contribute to the effective droplet size reduction of below 1 micron, usually between 100–300 nm. The SubMicron Emulsions as vehicles for transdermal delivery of Diazepam generate significant systemic activity of the drug as compared with regular creams or ointments. Transdermal delivery of Diazepam via SME formulations is very effective, and the activity may reach the range of parenteral delivery. A single application of Diazepam in SME cream to mice skin provides pronounced transdermal drug delivery and prolonged protective activity up to 6 hours.

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REFERENCES

  1. Y.W. Chien. Transdermal Drug Delivery. In: Novel Drug Delivery Systems, Marcel Dekker, Inc., New York, 1992, pp. 301–380

    Google Scholar 

  2. K. Egbaria, N. Weiner. Liposomes as a topical drug delivery system, Adv. Drug Del. Rev., 5:287–300 (1990)

    Google Scholar 

  3. D. Friedman, J. Schwarz and H. Aviv. Topical and transdermal delivery system utilizing submicron oil spheres. Patent Application PCT/US93/02800, publication number WO 93/18752 (30.09.93)

  4. L.S. Goodman, A. Gilman (Eds.), The Pharmacological Basis of Therapeutics, 4th edition, The Macmillan Company, New York, 1971, p. 178

    Google Scholar 

  5. A. Rolland, N. Wagner, A. Chatelus, B. Shroot and H. Schaefer. Site-Specific Drug Delivery to Pilosebaceous structures using polymeric microspheres. Pharm. Res., 12:1738–1744 (1993)

    Google Scholar 

  6. J. Du Plessis, N. Weiner and D.G. Muller. The influence of in vivo treatment of skin with liposomes on the topical absorption of a hydrophilic and a hydrophobic drug in vitro. Int. J. Pharmaceutics, 103:R1–R5 (1994).

    Google Scholar 

  7. B.W. Barry. Lipid-protein-partitioning theory of skin penetration enhancement. J. Controlled Release, 15:237–248 (1991).

    Google Scholar 

  8. J. Hadgraft, K.A. Walters and R.H. Guy. Epidermal lipids and topical drug delivery. Semin. Dermatol., 2:139–144 (1992).

    Google Scholar 

  9. D. Quan, H.I. Maibach. An electron spin resonance study: I. Effect of Azone® on 5-doxyl stearic acid-labeled human stratum corneum. Int. J. Pharmaceutics, 104:61–72 (1994).

    Google Scholar 

  10. R.O. Potts, G.M. Golden, M.L. Francoeur, V.H.W. Mak, and R.H. Guy, Mechanism and enhancement of solute transport across the stratum corneum. J. Contr. Release, 15:249–260 (1991)

    Google Scholar 

  11. T. De Vringer. Topical preparation containing a suspension of solid lipid particles. European Patent Application EP 0 506 197 A1, Bulletin 92/40 (30.09.92)

  12. R.H. Muller, C. Schwarz, A.Z. Mullen and W. Mehnert. Incorporation of lipophilic drugs and drug release profiles of solid lipid nanoparticles. Proceed. Intern. Symp. Control. Rel. Bioact. Mater., 21:146–147 (1994)

    Google Scholar 

  13. A.K. Banga and Y.W. Chien. Iontophoretic delivery of the drugs: Fundamentals, developments and biomedical applications. J. Control. Release, 7:1–24 (1988)

    Google Scholar 

  14. M.R. Prausnitz, V.G. Bose, R.S. Langer and J.C. Weaver. Transtissue molecular transport due to electroporation of skin. In: M. Blank (Ed.), Electricity and Magnetism in Biology and Medicine, San Francisco Press, San Francisco, 1993, pp. 122–124

    Google Scholar 

  15. D.I. Friedman, J.S. Schwarz and M. Weisspapir. Submicron Emulsion Vehicle For Enhanced Transdermal Delivery Of Steroidal And Non-steroidal Antiinflammatory Drugs. J. Pharm. Sci., in press

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Authors and Affiliations

  1. Pharmos Ltd., Kiryat Weizmann, 76326, Rehovot, Israel

    Joseph S. Schwarz, Michael R. Weisspapir & Doron I. Friedman

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  1. Joseph S. Schwarz
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  2. Michael R. Weisspapir
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  3. Doron I. Friedman
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Schwarz, J.S., Weisspapir, M.R. & Friedman, D.I. Enhanced Transdermal Delivery of Diazepam by Submicron Emulsion (SME) Creams. Pharm Res 12, 687–692 (1995). https://doi.org/10.1023/A:1016255408348

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  • DOI: https://doi.org/10.1023/A:1016255408348

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