Advertisement

European Journal of Clinical Pharmacology

, Volume 38, Supplement 1, pp S15–S19 | Cite as

Development of long-acting nitrate delivery systems

  • U. E. Jonsson
Article

Summary

In this paper pharmaceutical and biopharmaceutical aspects on the development of long-acting nitrate delivery systems are reviewed. Basic considerations and requirements are also discussed. Recent product development activities are presented, with an emphasis on nitroglycerin in transdermal form and oral isosorbide-5-mononitrate controlled-release formulations.

Key words

nitroglycerin isosorbide-5-mononitrate drug delivery systems biopharmaceutics 

References

  1. 1.
    Elbright GE (1914) The effects of nitroglycerin on those engaged in its manufacture. JAMA 62: 201–202Google Scholar
  2. 2.
    Needleman P, Lang S, Johnson EM (1972) Organic nitrates: relationship between biotransformation and rational angina pectoris therapy. J Pharmacol Exp Ther 181: 489–497PubMedGoogle Scholar
  3. 3.
    Thadani U, Fung HL, Darke AC, Parker JO (1982) Oral isosorbide dinitrate in angina pectoris: comparison of duration of action and dose-response relation during acute and sustained therapy. Am J Cardiol 49: 411–419Google Scholar
  4. 4.
    Flaherty JT (1989) Nitrate tolerance. A review of the evidence. Drugs 37: 523–550PubMedGoogle Scholar
  5. 5.
    Fung H-L, Chong S, Kowaluk E (1989) Mechanisms of nitrate action and vascular tolerance. Eur Heart J 10 [Suppl A]: 2–6Google Scholar
  6. 6.
    Carboni GP, Lahiri A, Cashman PMM, Raftery EB (1987) Ambulatory heart rate and ST-segment depression during painful and silent myocardial ischemia in chronic stable angina pectoris. Am J Cardiol 59: 1029–1034PubMedGoogle Scholar
  7. 7.
    Nigam R, Loveday BJ, Grainger SL, Maxton DG (1986) Three times daily or 8-hourly. J R Soc Med 79: 15–16Google Scholar
  8. 8.
    Norell SE (1982) Pilocarpine t. i. d.-how is it taken? Pharm Int 3: 123–125Google Scholar
  9. 9.
    Abshagen U, Betzien G, Endele R, Kaufmann B (1981) Pharmacokinetics of intravenous and oral isosorbide-5-mononitrate. Eur J Clin Pharmacol 20: 269–275PubMedGoogle Scholar
  10. 10.
    Laufen H, Wildfeuer A (1987) Absorption of isosorbide-5-nitrate from the gastrointestinal tract. In: Rietbrock N, Woodcock BG, Staib AH, Loew D (eds) Methods in clinical pharmacology, no 7. Vieweg & Sohn, Braunschweig, pp 76–81Google Scholar
  11. 11.
    Jonsson UE (1987) Various administration forms of nitrates and their possibilities. Drugs 33 [Suppl 4]: 23–31PubMedGoogle Scholar
  12. 12.
    Monkhouse DC, Hua AS (1988) Transdermal drug delivery — problems and promises. Drug Dev Ind Pharm 14: 183–209Google Scholar
  13. 13.
    Abrams J (1989) Transdermal nitroglycerin in angina pectoris. Eur Heart J 10 [Suppl A]: 11–19Google Scholar
  14. 14.
    Gatlin KA (1985) Comparative patient preference for 2 transdermal nitroglycerin patches. Curr Ther Res 38: 733–737Google Scholar
  15. 15.
    Hougham AJ, Hawkinson RW, Crowley JK et al (1989) Improved skin adherence and patient acceptance in a new transdermal nitroglycerin delivery system. Clin Ther 11: 23–31PubMedGoogle Scholar
  16. 16.
    Wick KA, Wick SM, Hawkinson RW, Holtzman JL (1989) Adhesion-to-skin performance of a new transdermal nitroglycerin adhesive patch. Clin Ther 11: 417–424PubMedGoogle Scholar
  17. 17.
    Ridout G, Santus GC, Guy RH (1988) Pharmacokinetic considerations in the use of newer transdermal formulations. Clin Pharmacokinet 15: 114–131PubMedGoogle Scholar
  18. 18.
    Cowan JC, Bourke JP, Reid DS, Julian DG (1987) Prevention of tolerance to nitroglycerin patches by overnight removal. Am J Cardiol 60: 271–275PubMedGoogle Scholar
  19. 19.
    Wolff H-M, Bonn R (1989) Principles of transdermal nitroglycerin administration. Eur Heart J 10 [Suppl A]: 26–29PubMedGoogle Scholar
  20. 20.
    Parker JO (1989) Antianginal efficacy of a new nitroglycerin patch. Eur Heart J 10 [Suppl A]: 43–49Google Scholar
  21. 21.
    Wiegand A, Bauer KH, Bonn R, Trenk D, Jähnchen E (1989) Time course of the hemodynamic efficacy of nitroglycerin released discontinuously from a transdermal therapeutic system. Eur J Clin Pharmacol 36 [Suppl A]: A101Google Scholar
  22. 22.
    Fischer W, Boertz A, Davis SS et al (1987) Investigation of the gastrointestinal transit and in vivo drug release of isosorbide-5nitrate pellets. Pharm Res 4: 480–485PubMedGoogle Scholar
  23. 23.
    Heidemann R, Gracien E, Menke G, Rietbrock N (1987) Bioverfügbarkeit von retardierten und nicht-retardierten Isosorbid-5-nitrat-Präparaten. Dtsch Med Wochenschr 112: 719–722PubMedGoogle Scholar
  24. 24.
    Neugebauer G, Akpan W, Stemmle B, Jaeger H, Mosberg H, Lutz D (1989) Performance of a slow-release formulation of isosorbide-5-mononitrate (ISMO® retard). Int J Clin Pharmacol Ther Toxicol 27: 34–38PubMedGoogle Scholar
  25. 25.
    Skutta T, Böttcher B, Brandt L (1989) Pharmakokinetisches Profil and Bioverfügbarkeit einer neuen galenischen Zubereitung von Isosorbid-5-mononitrat retard. Arzneimittelforschung 39: 507–511PubMedGoogle Scholar
  26. 26.
    Zerbe H, Luckow V, Cawello W, Cordes G (1985) Isosorbide-5nitrate sustained-release pellets — an example of computer-supported drug development. Pharm Res 2: 30–36Google Scholar
  27. 27.
    Ingendaay A, Klein G, Rehm KD, Töberich H, Vanscheidt W (1987) Vergleichende Pharmakokinetic retardierter Mononitratpräparate. Münch Med Wochenschr 129: 34–36Google Scholar
  28. 28.
    Sjögren J (1971) Studies on a sustained release principle based on an inert plastic matrix. Acta Pharm Suec 8: 153–168PubMedGoogle Scholar
  29. 29.
    Nyberg G, Carlens P, Lindström E et al (1986) The effect of isosorbide-5-mononitrate (5-ISMN) Durules® on exercise tolerance in patients with exertional angina pectoris. A placebo controlled study. Eur Heart J 7: 835–842PubMedGoogle Scholar
  30. 30.
    Wisenberg G, Roks C, Nichol P, Goddard MD (1989) Sustained effect of and lack of development of tolerance to controlled-release isosorbide-5-mononitrate in chronic stable angina pectoris. Am J Cardiol 64: 569–576PubMedGoogle Scholar

Copyright information

© Springer-Verlag 1990

Authors and Affiliations

  • U. E. Jonsson
    • 1
  1. 1.Pharmaceutical Research and DevelopmentMölndalSweden

Personalised recommendations