Journal of Pharmaceutical Investigation

  • 제35권5호
  • /
  • Pages.329-332
  • /
  • 2005
  • /
  • 2093-5552(pISSN)
  • /
  • 2093-6214(eISSN)
한국약제학회 (The Korean Society of Pharmaceutical Sciences and Technology)
권호 표지
DOI QR코드

DOI QR Code

In vitro and In vivo Evaluation of Novel Gel Formulations of Testosterone for Transdermal Delivery

  • 발행 : 2005.10.20
PDF 다운로드
⟨ 이전 논문 다음 논문 ⟩

초록

HPMC-based novel gel formulations for the transdermal delivery of testosterone (TS) were developed, and the effect of various skin permeation enhancers was studied in vitro and in vivo. In vitro hairless mouse skin permeation of TS from the gel was investigated using Keshary-Chien diffusion cells for 8 hours at $37^{\circ}C$. In vivo plasma concentration profiles of TS after applying the gel on the abdominal skin of rat were determined using a commercial radioimmunoassay kit. Hairless mouse skin permeation of TS increased with the addition of permeation enhancers both in vitro and in vivo. Combination of diethanolamine (2%) and N-methylpyrrolidone (NMP, 6%) was the most effective among tested. Plasma concentration of TS significantly increased for at least 24 hours with the addition of diethanolamine and NMP. These results suggest the feasibility of the development of a HPMC-based gel formulation for the transdermal delivery of TS.

키워드

참고문헌

  1. J.G. Hardman and L.E. Limbird, A Goodman and Gilman's the pharmacological basis of therapeutics, 9th ed., Macmillan, London, pp. 1459-1485 (1996)
  2. R.L. Rosenfield, Role of androgens in growth and development of the fetus, child, and adolescent. Adv. Pediatr., 19, 172-213 (1972)
  3. A.R. Gennaro, Remington: The Science and Practice of Pharmacy, 20th ed., Lippincott Williams & Wilkins, Philadelphia, U.S.A., pp. 1391 (2000)
  4. S. Satyannrana, S. Ganaga and J. Singh, Transport through rat skin from transdermal patch formulations. Pharmazie, 48, 467-468 (1993)
  5. T.M. Morgan, B.L. Reed and B.C. Finnin, Enhanced skin permeation of sex hormones with novel topical spray vehicles. J. Pharm. Sci., 87, 1213-1218 (1998) https://doi.org/10.1021/js980025k
  6. T.M. Morgan, R.A. Parr, B.L. Reed and B.C. Finnin, Enhanced transdermal delivery of sex hormones in swine with a novel topical aerosol. J. Pharm. Sci., 87(1), 1219-1225 (1998) https://doi.org/10.1021/js980026c
  7. B. Salehian, C. Wand, G. Alexander, T. Davidson, V. McDonald, N. Berman, R.E. Dudley, F. Zikl and R.S. Verdloff, Pharmacokinetics, bioefficacy and safety of sublingual tesosterone cyclodextrin in hypogonadal men: comparison to testosterone enanthate-A clinical research center study. J. Clin. Endocr. Metab., 80(12), 3567-3575 (1995) https://doi.org/10.1210/jc.80.12.3567
  8. D.J. Kesler, D.C. Christenson and M.E. Wallace, The effect of esterification on their release of testosterone and estradiol from silicone implants. Drug Dev. Ind. Pharm., 22(3), 275-279 (1996) https://doi.org/10.3109/03639049609058572
  9. A.C. William and B.W. Barry, Skin permeation enhancers. Crit. Rev. Ther. Drug, 9, 305-353 (1992)
  10. K. Sugibayashi, S. Nakyama, S. Seki, K. Hosoya and Y. Morimoto, Mechanism of skin penetration-enhancing effect by laurocapram. J. Pharm. Sci., 81, 58-64 (1992) https://doi.org/10.1002/jps.2600810112
  11. N.M. An, D, D. Kim, Y.H. Shin and C.H. Lee, Development of a novel soft hydrogel for the transdermal delivery of testosterone. Drug Devel. Ind. Pharm., 29, 99-105 (2003) https://doi.org/10.1081/DDC-120016688
  12. M.K. Kim, H.Z., C.H. Lee and D.D. Kim, Formulation of a reservoir-type testosterone transdermal delivery system. Int. J. Pharm., 219, 51-59 (2001) https://doi.org/10.1016/S0378-5173(01)00631-7
  13. H.Z., C.H. Lee, S.J. Chung, C.K. Shim and D.D. Kim, In, vitro and in vivo evaluation of a novel non-scrotal matrix-type transdermal delivery system of testosterone. Drug Dev. Ind. Pharm., 31, 257-261 (2005) https://doi.org/10.1081/DDC-52044
  14. B.J. Anungst, J.A. Blake and M.A. Hussain, Contributions of drug solubilization, partitioning, barrier disruption, and solvent permeation to the enhancement of skin permeation of various compounds with fatty acids and amines. Pharm. Res., 7, 712-718 (1990) https://doi.org/10.1023/A:1015859320604
  15. A. Koizumi, M. Fujiu, M. Kondoh and Y. Watanabe, Effect of N-methyl-2-pyrrolidone on skin permeation of estradiol. Eur. J. Pharm. Biopharm., 57, 473-478 (2004) https://doi.org/10.1016/j.ejpb.2003.12.006
  16. L. Kikwai, R.J. Babu, N. Kanikkannan and M. Singh, Preformulation stability of Spantide II, a promising topical anti-inflmatory agent for the treatment of psoriasis and contact dermatitis. J. Pharm. Pharmacol., 56, 19-25 (2004) https://doi.org/10.1111/j.2042-7158.2004.tb02573.x
  17. M. Fuju, M. Bouno, S. Fujita, M. Yoshida, Y. Watanabe and M. Matsumoto, Preparation of griseofulvin for topical application using N-methyl-2-pyrrolidone. Bio. Pharm. Bull., 23, 1341-1345 (2000) https://doi.org/10.1248/bpb.23.1341
  18. P.J. Lee, R. Langer and V.P. Shastri, Role of n-methyl pyrrolidone in the enhancement of aqueous phase transdermal transport. J. Pharm. Sci., 94, 912-917 (2005) https://doi.org/10.1002/jps.20291
  19. J.E. Royland, L.J. Weber and M. Fitzpatrick, Testes size and testosterone levels in a model for weightlessness. Life Sci., 54, 545-554 (1994) https://doi.org/10.1016/0024-3205(94)90005-1