YAKHAK HOEJI (약학회지)

The Pharmaceutical Society of Korea (대한약학회)
권호 표지

Preparation and Evaluation of $PGE_1$ Urethral Suppositories

$PGE_1$ 요도좌제의 제조 및 평가

  • Park Somin (College of Pharmacy, Ewha Womans University) ;
  • Choi Myeongsin (College of Pharmacy, Ewha Womans University) ;
  • Han Kyuwon (College of Pharmacy, Ewha Womans University) ;
  • Kim Kil-Soo (College of Pharmacy, Ewha Womans University)
  • 박소민 (이화여자대학교 약학대학) ;
  • 최명신 (이화여자대학교 약학대학) ;
  • 한규원 (이화여자대학교 약학대학) ;
  • 김길수 (이화여자대학교 약학대학)
  • Published : 2005.08.01
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Abstract

[ $PGE_1$ ] is an endogenous substance of potent vasodialator as well as inhibitor of platelet aggregation. It has been used therapeutically in peripheral arterial occlusive disease and impotence. Intracavernous injection of $PGE_1$ for erectile dysfunction has been established for several years as a treatment option for erectile dysfunction of diverse etiologies, but this mode of administration is limited by penile discomfort, pain at the injection site, inconvenience and noncompliance. As the matter of worse, the $\beta-hydroxy$ moiety of $PGE_1$ is extremely susceptible to dehydration in solution to give inactive $PGA_1$ and $PGB_1$. For the improvement of stability, rapid absorption at action site and the convenience of application, $PGE_1$ was formulated as urethral suppositories of three types of formulations, such as PEG, witepsol, and the mixture of PEG and witepsol. The stability test of $PGE_1$ and the release test in urinary suppositories were performed. Futhermore, the effect of enhancers and vehicle composition on the penetration of $PGE_1$ through excised rat skin was evaluated by permeability coefficient and enhancement ratio.

Keywords

References

  1. Montorsi, F., Guazzoni, G., Rigatti, P. and Pozza, G. : Pharmacological management of erectile dysfunction. Drugs 50, 465 (1995) https://doi.org/10.2165/00003495-199550030-00005
  2. Goldschalk, M. F., Chen, J., Katz, P. G. and Mulligan, T. : Treatment of erectile failure with prostaglandin $E_1$ : a doubleblind, placebo-controlled, dose-response study. J. Urology 151, 1530 (1994) https://doi.org/10.1016/S0022-5347(17)35293-X
  3. Martinez-Pineiro, L. M., Tello, J. L., Alonso Dorrego, J. M., Cisneros, J., Cuervo, E. and Martinez-Pineiro, J. A. : Preliminary results of a comparative study with intracavernous sodium nitroprusside and prostaglandin $E_1$ in patients with erectile dysfunction. J. Urology 153, 1487 (1995) https://doi.org/10.1016/S0022-5347(01)67441-X
  4. Chen, J., Godschalk, M., Katz, P. G. and Mulligan, T. : The lowest effective dose of prostaglandin $E_1$ as treatment for erectile dysfunction. J. Urology 153, 80 (1995) https://doi.org/10.1097/00005392-199501000-00028
  5. Prost, H., Review Article: The nationale for prostagladin $E_1$ in erectile failure: a survey of worldwide experience. J. Urol. 155, 802 (1996) https://doi.org/10.1016/S0022-5347(01)66315-8
  6. Montague, D. K. et al. : Clinical guidelines panel on erectile function: summary report on the treatment of organic erectile dysfunction. J. Urol. 156, 2007 (1996)
  7. Foldvari, M., Oguejiofor, C.J.N., Wilson, T. W., Afridi, S. K. and Rudel, T. A. : Transcutaneous delivery of prostaglandin $E_1$ : in vitro and laser doppler flowmetry study.J. Pharm. Sci. 87, 721 (1998) https://doi.org/10.1021/js9702980
  8. Kim, E, D. and Macvary, K. T. : Topical prostagladin $E_1$ for the treatment of erectile dysfunction. J. Urology 153, 1828 (1995) https://doi.org/10.1016/S0022-5347(01)67323-3
  9. Mizusnima, Y. : Lipo-prostaglandin preparations. Prostagl. Leukotr. Essent. Fatty Acids 42, 1 (1991) https://doi.org/10.1016/0952-3278(91)90058-D
  10. Lakin, M. M., Montague, D. K., Medendorps, V. B. and Schover, L. R. : Intracavernous Injection therapy: analysis of results and complictions. J. Urol. 143, 1138 (1990) https://doi.org/10.1016/S0022-5347(17)40208-4
  11. Linet, O. I. and Ogrninc, F. G. : Efficiency and safety of intracavernous alprostadil in men with erectile dysfunction. The New Engl. J. Med. 334, 873 (1996) https://doi.org/10.1056/NEJM199604113341519
  12. Waldhauser, M. and Schramek, P. : Efficiency and side effect of prostagladin $E_1$ in the treatment of erectile dysfunction. J. Urol. 140, 525(1998)
  13. Harin, P. A., Wayne, J. G. and Fran, E. K. : Treatement of men with erectile dysfunction with transurethral Alprostadil. The New Eng. J Med. 336, 1 (1997) https://doi.org/10.1056/NEJM199701023360101
  14. 유도라 : 반고형 외용제제에서의 $PGE_1$의 안정화 및 투과촉진에 관한 연구. 이화여자대학교 대학원 석사학위 청구논문(1998)
  15. Yamamura, K. : High-performance liquid chromatographic assay prostaglandin $E_1$ in various ointment vehicles.J. Control. Rel., 303, 165 (1984)
  16. Shulman, N. H. and Fyfe, R. K. : Shelf-life determination of prostaglandin $E_1$ injections, J. Clin. Pharm. The. 20, 41 (1995) https://doi.org/10.1111/j.1365-2710.1995.tb00624.x
  17. Blaey, C. J. and Fokkens, J. G. : Drug release from suppositories. Pharmaceutical Res. (1985)
  18. Sloan, K. B., Siver, K. G. and Koch, S. A. M. : The effect of vehicle on the diffusion of salicylic acid through hairless mouse skin. J. Pharm. Sci. 75, 744 (1986) https://doi.org/10.1002/jps.2600750804
  19. Jain, G. K, Kaul, J. L. and Agrawal, S. S. : In vitro transdermal delivery of atenolol using mouse and guinea pig. Indian J. Exp. Biol. 31, 691 (1993)
  20. Ghosh, T. K., Gokhale, R. D. and Chiao, C. S. : In-vitro assessment of a matrix system of levobunolol. J. Pharm. Pharmacol. 44, 512 (1992) https://doi.org/10.1111/j.2042-7158.1992.tb03656.x
  21. Jain, G. K. and Agrawal, S. S. : In vitro percutaneous absorption of verapamil. Indian J. Exp. Biol. 34, 475 (1996)
  22. Shulman, N. H. and Fyfe, R. K. : Shelf-life determination of prostaglandin $E_1$ injections. J. Clin. Pharm. The. 20, 41 (1995) https://doi.org/10.1111/j.1365-2710.1995.tb00624.x
  23. Monkhouse, D. C., Campenl., V. and Aguiar; A. J. : Kinetics of dehydration and isomerization of prostaglandins $E_1$ and $E_2$. J. Pharm. Sci. 62, 576 (1973) https://doi.org/10.1002/jps.2600620406
  24. Stehle, R. G. and Oesterling, T. O. : Stability of prostaglandin $E_1$ and dinoprostone (prostaglandin $E_2$) under strongly acidic and basic conditions. J. Pharm. Sci. 66(11), 1590 (1977) https://doi.org/10.1002/jps.2600661123
  25. Younger; E. W. and Szabo, R. M. : The stability of prostaglandin $E_1$ in dilute physiological solution at 37 degrees C. Prostaglandins 31(5), 923 (1986) https://doi.org/10.1016/0090-6980(86)90024-9
  26. Teagarden, D. L., Anderson, B. D. and Petre, W. J. : Dehydration kinetics of prostaglandin $E_1$ in a lipid emulsion. Pharm. Res. 6, 210 (1989) https://doi.org/10.1023/A:1015909432300
  27. Barry, B. W. : Mode of action of penetration enhancers in human skin. J. Control. Rel. 6, 85 (1987) https://doi.org/10.1016/0168-3659(87)90066-6
  28. Singh, S. K., Durrani, M. J., Reddy, I. K. and Khan, M. A. : Effect of permeation enhancers on the release of ketoprofen through transdermal drug delivery systems. Pharmazie. 51, 741 (1996)
  29. Hanif, R. M., Qineng, P. and Zhan, G. : Penetration enhancing effect of tetrahydrogeraniol on the percutaneous absorption of 5-fluorouracil from gels in excised rat skin. J. Control Release 55, 297 (1998) https://doi.org/10.1016/S0168-3659(98)00062-5
  30. Green, P. G., Guy, R. H. and Hadgraft, J. : In vitro and in vivo enhancement of skin permeation with oleic and lauric acids. Int. J. Pharm. 48, 103 (1988) https://doi.org/10.1016/0378-5173(88)90252-9
  31. Naik, A. L., Pechtold, A. R. M., Potts, R. O. and Guy, R. R. : Mechanism of oleic acid-induced skin penetration enhancement in vivo in humans. J. Control. Rel. 37, 299 (1995) https://doi.org/10.1016/0168-3659(95)00088-7
  32. Elias, P. M. : Epidermal lipids, barrier function and desquamation. J. Invest. Dermatol. 80, Suppl., 44 (1983)
  33. Bhatt, P. P., Rytting, J. H., and Topp, E. M. : Influence of Azone? and lauryl alcohol on the transport of acetaminophen and ibuprofen through shed snake skin. Int. J. Pharm., 72, 219 (1991) https://doi.org/10.1016/0378-5173(91)90111-Z