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Nicotine delivery systems

How far has technology come?

  • Technology in Practice
  • Published:
American Journal of Drug Delivery

Abstract

Due to the profound mortality associated with tobacco use, effective treatments for tobacco dependence are needed. Currently, the most widely available pharmacotherapy is nicotine replacement therapy (NRT). This paper will review the state of the science and public health policy regarding NRT.

Several formulations have been developed for delivering nicotine into the body, including nicotine patch, gum, oral inhaler, nasal spray, and lozenge. Nicotine patches deliver nicotine at a relatively steady rate and are applied once daily. All other forms are taken on a periodic basis, multiple times per day. All of these products, except the nasal spray, deliver nicotine through the oral mucosa. New formulations are currently in the development phase. There are also several ways in which currently available formulations could be modified to improve delivery. The future of NRT may include the development of a true pulmonary inhaler, products for long-term maintenance, products for reduced smoking, products for acute use, and the tailoring of treatments for individual smokers. Nicotine replacement medications have been shown to be efficacious in dozens of clinical trials, and have had an impact on public health by assisting thousands of smokers to quit smoking. The over-the-counter marketing of nicotine patches and gum allows smokers ready access to these medications, and has led to an increase in product use and successful cessation compared with prescription-only marketing. The wide menu of NRT medications for smoking cessation gives patients and healthcare professionals options for treatment. However, whereas NRT medications double quit rates compared with unassisted attempts, there is clearly much to be done to improve the proportion of quitters who use evidence-based treatment, their use of the products, and the usability and inherent efficacy of NRT.

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Notes

  1. The use of tradenames is for product identification purposes only and does not imply endorsement.

References

  1. The World Bank. Curbing the epidemic: governments and the economics of tobacco control. Washington, DC: The International Bank for Reconstruction and Development/The World Bank, 1999

    Google Scholar 

  2. Royal College of Physicians. Nicotine addiction in Britain: a report of the Tobacco Advisory Group of the Royal College of Physicians. London: Royal College of Physicians of London, 2000

    Google Scholar 

  3. Department of Health and Human Services. Reducing tobacco use: a report of the Surgeon General. Atlanta (GA): US Department of Health and Human Services, Office on Smoking and Health, 2000

    Google Scholar 

  4. US Department of Health and Human Services. The health consequences of smoking: nicotine addiction. Rockville (MD): US Government Printing Office, 1988

    Google Scholar 

  5. Fiore MC, Bailey WC, Cohen SJ, et al. Treating tobacco use and dependence: clinical practice guideline. Rockville (MD): US Department of Health and Human Services, Public Health Service, 2000

    Google Scholar 

  6. Fiore MC. A clinical practice guideline for treating tobacco use and dependence. JAMA 2000; 283: 3244–54

    Article  Google Scholar 

  7. World Health Organization. The ICD-10 classification of mental behavioural disorders. Geneva: World Health Organization, 1992

    Google Scholar 

  8. American Psychiatric Association. Nicotine dependence and substance use disorders: diagnostic and statistic manual of mental disorders. Washington, DC: American Psychiatric Association, 1994

    Google Scholar 

  9. Hughes JR, Hatsukami D. Signs and symptoms of tobacco withdrawal. Arch Gen Psychiatry 1986; 43: 289–94

    Article  PubMed  CAS  Google Scholar 

  10. Pickworth WB, Heishman SJ, Henningfield JE. Relationships between EEG and performance during nicotine withdrawal and administration. In: Domino EF, editor. Brain Imaging of Nicotine and Tobacco Smoking. Ann Arbor (MI); NPP Books, 1995: 275–87

    Google Scholar 

  11. Ernst M, Matochik JA, Heishman SJ, et al. Effect of nicotine on brain activation during performance of a working memory task. Proc Natl Acad Sci USA 2001; 98: 4728–33

    Article  PubMed  CAS  Google Scholar 

  12. Heishman SJ, Taylor RC, Henningfield JE. Nicotine and smoking: a review of effects on human performance. Exp Clin Psychopharmacol 1994; 2: 345–95

    Article  CAS  Google Scholar 

  13. US Department of Health and Human Services. The health consequences of smoking: nicotine addiction: a report of the Surgeon General. Washington, DC: US Government Printing Office, 1988

    Google Scholar 

  14. Piasecki TM, Fiore MC, Baker TB. Profiles in discouragement: two studies of variability in the timecourse of smoking withdrawal symptoms. J Abnorm Psychol 1998; 107: 238–51

    Article  PubMed  CAS  Google Scholar 

  15. Henningfield JE. Nicotine medications for smoking cessation. N Engl J Med 1995; 333: 1196–203

    Article  PubMed  CAS  Google Scholar 

  16. American Psychiatric Association. Practice guideline for the treatment of patients with nicotine dependence. Am J Psychiatry 1996; 153: 1–31

    Google Scholar 

  17. Benowitz NL. Nicotine replacement therapy: what has been accomplished: can we do better. Drugs 1993; 45: 157–70

    Article  PubMed  CAS  Google Scholar 

  18. Sliagy C, Lancaster T, Stead L, et al. Nicotine replacement therapy for smoking cessation (Cochrane Review). The Cochrane Database of Systematic Reviews. Available in The Cochrane Library [database on disk and CD ROM]. Updated quarterly. The Cochrane Collaboration; issue 4. Oxford: Update Software, 2002: CD000146

    Google Scholar 

  19. Benowitz NL. Clinical pharmacology of transdermal nicotine. Eur J Pharm Biopharm 1995; 41: 168–74

    CAS  Google Scholar 

  20. Gorsline J. Nicotine pharmacokinetics of four nicotine transdermal systems. Health Values 1993; 17(2): 20–4

    Google Scholar 

  21. Fant RV, Henningfield JE, Shiffman S, et al. A pharmacokinetic crossover study to compare the absorption characteristics of three transdermal nicotine patches. Pharmacol Biochem Behav 2000; 67: 479–82

    Article  PubMed  CAS  Google Scholar 

  22. Hajek P, West R, Foulds J, et al. Randomized comparative trial of nicotine polacrilex, a transdermal patch, nasal spray, and an inhaler. Arch Intern Med 1999; 159: 2033–8

    Article  PubMed  CAS  Google Scholar 

  23. Tiffany ST, Cox LS, Elash CA. Effects of transdermal nicotine patches on abstinence-induced and cue-elicited craving in cigarette smokers. J Consult Clin Psychol 2000; 68: 233–40

    Article  PubMed  CAS  Google Scholar 

  24. Shiffman S, Engberg JB, Paty JA, et al. A day at a time: predicting smoking lapse from daily urge. J Abnorm Psychol 1997; 106: 104–16

    Article  PubMed  CAS  Google Scholar 

  25. Shiffman S, Gnys M, Richards TJ, et al. Temptations to smoke after quitting: a comparison of lapsers and maintainers. Health Psychol 1996; 15: 455–61

    Article  PubMed  CAS  Google Scholar 

  26. Benowitz NL, Jacob III P, Savanapridi C. Determinants of nicotine intake while chewing nicotine polacrilex gum. Clin Pharmacol Ther 1987; 41: 467–73

    Article  PubMed  CAS  Google Scholar 

  27. Tonnesen P, Fryd V, Hansen M, et al. 2 and 4mg nicotine chewing gum and group counseling in smoking cessation: an open, randomized, controlled trial with a 22 month follow-up. Addict Behav 1988; 13: 17–27

    Article  PubMed  CAS  Google Scholar 

  28. Herrera N, Franco R, Herrera L, et al. Nicotine gum, 2 and 4mg, for nicotine dependence: a double-blind placebo-controlled trial within a behavior modification support program. Chest 1995; 106: 447–51

    Article  Google Scholar 

  29. Shiffman S, Rolf CN, Hellebusch SJ, et al. Real-world efficacy of prescription and over-the-counter nicotine replacement therapy. Addiction 2002; 97: 505–16

    Article  PubMed  Google Scholar 

  30. Shiffman S, Gorsline J, Gorodetzky CW. Efficacy of over-the-counter nicotine patch. Nicotine Tob Res 2002; 4: 477–83

    Article  PubMed  CAS  Google Scholar 

  31. Shiffman S, Gitchell J, Pinney JM, et al. Public health benefit of over-the-counter nicotine medications. Tob Control 1997; 6: 306–10

    Article  PubMed  CAS  Google Scholar 

  32. Russell MAH, Merriman R, Stapleton J. Effect of nicotine chewing gum as an adjunct to general practitioner’s advice against smoking. BMJ 1983; 10: 1782–5

    Article  Google Scholar 

  33. Benowitz NL, Jacob P. Daily intake of nicotine during cigarette smoking. Clin Pharmacol Ther 1984; 35: 499–504

    Article  PubMed  CAS  Google Scholar 

  34. Henningfield JE, Radzius A, Cooper TM, et al. Drinking coffee and carbonated beverages blocks absorption of nicotine from nicotine polacrilex gum. JAMA 1990; 264: 1560–4

    Article  PubMed  CAS  Google Scholar 

  35. Shiffman S, Shadel WG, Niaura R, et al. Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving. Psychopharmacology (Berl) 2003; 166(4): 343–50

    CAS  Google Scholar 

  36. Cohen LM, Collins FL, Britt DM. The effect of chewing gum on tobacco withdrawal. Addict Behav 1997; 22: 769–73

    Article  PubMed  CAS  Google Scholar 

  37. Shiffman S, Dresler CM, Hajek P, et al. Efficacy of a nicotine lozenge for smoking cessation. Arch Intern Med 2002; 162: 1267–76

    Article  PubMed  CAS  Google Scholar 

  38. Choi J, Dresler CM, Norton MR, et al. The pharmacokinetic characteristics of the NPA lozenge [abstract]. Annual Meeting of the Society for Research on Nicotine and Tobacco; 2000 Feb 18–20; Savannah

  39. Heatherton TF, Kozlowski LT, Frecker RC, et al. The Fagerstrom test for nicotine dependence: a revision of the Fagerstrom Tolerance Questionnaire. Br J Addict 1991; 86: 1119–27

    Article  PubMed  CAS  Google Scholar 

  40. Molander L, Lunell E. Pharmacokinetic investigation of a nicotine sublingual tablet. Eur J Clin Pharmacol 2001; 56: 813–9

    Article  PubMed  CAS  Google Scholar 

  41. Molander L, Lunell E, Andersson SB, et al. Dose released and absolute bioavailability of nicotine from a nicotine vapor inhaler. Clin Pharmacol Ther 1996; 59: 394–400

    Article  PubMed  CAS  Google Scholar 

  42. Bergstrom M, Nordberg A, Lunell E, et al. Regional deposition of inhaled 11C-nicotine vapor in the human airway as visualized by positron emission tomography. Clin Pharmacol Ther 1995; 57: 309–17

    Article  PubMed  CAS  Google Scholar 

  43. Lunell E, Molander L, Andersson SB. Temperature dependency of the release and bioavailability of nicotine from a nicotine vapour inhaler; in vitro/in vivo correlation. Eur J Pharmacol 1997; 52: 495–500

    Article  CAS  Google Scholar 

  44. Schneider NG, Lunell E, Olmstead RE, et al. Clinical pharmacokinetics of nasal nicotine delivery: a review and comparison to other nicotine systems. Clin Pharmacokinet 1996; 31: 65–80

    Article  PubMed  CAS  Google Scholar 

  45. Hurt RD, Offord KP, Croghan IT, et al. Temporal effects of nicotine nasal spray and gum on nicotine withdrawal symptoms. Psychopharmacology (Berl) 1998; 140: 98–104

    Article  CAS  Google Scholar 

  46. US Department of Health and Human Services, Food and Drug Administration. Regulations restricting the sale and distribution of cigarettes and smokeless tobacco to protect children and adolescents; final rule. Federal Register 1996; 61: 44396–5318

    Google Scholar 

  47. Schuh KJ, Schuh LM, Henningfield JE, et al. Nicotine nasal spray and vapor inhaler: abuse liability assessment. Psychopharmacology (Berl) 1997; 130: 352–61

    Article  CAS  Google Scholar 

  48. Westman EC, Tomlin KF, Perkins CE, et al. Oral nicotine solution: single dose pharmacokinetic study [abstract]. Annual Meeting of the Society for Research on Nicotine and Tobacco; 2001 Mar 23–25; Seattle

  49. Westman EC, Tomlin KF, Perkins CE, et al. Oral nicotine solution for smoking cessation: a pilot tolerability study. Nicotine Tob Res 2001; 3: 391–6

    Article  PubMed  CAS  Google Scholar 

  50. D’Orlando KJ, Fox BS. The straw nicotine oral delivery system: safety and pharmacokinetics of single and repeated dosing [abstract]. Annual Meeting of the College on Problems on Drug Dependence; 2002 Jun 7–13; Quebec City

  51. Zobrist H, Marriot JG, Gilbert R, et al. Preliminary eight week safety and efficacy of oral transmucosal nicotine (OT-nicotine) compared to patch and gum for smoking cessation [abstract]. Annual Meeting of the Society for Research on Nicotine and Tobacco; 1997 Jun 13–14; Nashville

  52. Zevin S, JacobIII P, Benowitz NL. Dose-related cardiovascular and endocrine effects of transdermal nicotine. Clin Pharmacol Ther 1998; 64: 87–95

    Article  PubMed  CAS  Google Scholar 

  53. Tonnesen P, Paoletti P, Gustavsson G, et al. Higher dosage nicotine patches increase one-year smoking cessation rates: results from the European Collaborative European Anti-Smoking Evaluation (CEASE) trial. Eur Respir J 1999; 13: 238–46

    Article  PubMed  CAS  Google Scholar 

  54. Transdermal Nicotine Study Group. Transdermal nicotine for smoking cessation. JAMA 1991; 266: 3133–8

    Article  Google Scholar 

  55. Jorenby DE, Smith SS, Fiore MC, et al. Varying nicotine patch dose and type of smoking cessation counseling. JAMA 1995; 274: 1347–52

    Article  PubMed  CAS  Google Scholar 

  56. Hughes JR, Lesmes GR, Hatsukami DK, et al. Are higher doses of nicotine replacement more effective for smoking cessation. Nicotine Tob Res 1999; 1: 169–74

    Article  PubMed  CAS  Google Scholar 

  57. Sweeney CT, Fant RV, Fagerstrom KO, et al. Combination nicotine replacement therapy for smoking cessation: rationale, efficacy and tolerability. CNS Drugs 2001; 15: 453–67

    Article  PubMed  CAS  Google Scholar 

  58. Kornitzer M, Boutsen M, Dramaix M, et al. Combined use of nicotine patch and gum in smoking cessation: a placebo-controlled clinical trial. Prev Med 1995; 24: 41–7

    Article  PubMed  CAS  Google Scholar 

  59. Fagerstrom KO, Schneider NG, Lunell E. Effectiveness of nicotine patch and nicotine gum as individual versus combined treatments for tobacco withdrawal symptoms. Psychopharmacology (Berl) 1993; 111: 271–7

    Article  CAS  Google Scholar 

  60. Puska P, Korhonen H, Vartiainen E, et al. Combined use of nicotine patch and gum compared with gum alone in smoking cessation: a clinical trial in North Karelia. Tob Control 1995; 4: 231–5

    Article  Google Scholar 

  61. Blondal T, Gudmundsson LJ, Olafsdottir I, et al. Nicotine nasal spray with nicotine patch for smoking cessation: randomised trial with six year follow up. BMJ 1999; 318: 285–9

    Article  PubMed  CAS  Google Scholar 

  62. Shiftman S, Shadel WG, Niaura R, et al. Efficacy of acute administration of nicotine gum in relief of cue-provoked cigarette craving. Psychopharmacology (Berl) 2003; 166(4): 343–50

    Google Scholar 

  63. Shiffman S, Paty JA, Gnys M, et al. First lapses to smoking: within-subjects analysis of real-time reports. J Consult Clin Psychol 1996; 64: 366–79

    Article  PubMed  CAS  Google Scholar 

  64. Cherukuri SR, Pinney JM, Henningfield JE, et al. Medicated chewing gum delivery system for nicotine. US Patent 6,344,222. 2002 Feb 5

  65. Pinney JM, Henningfield JE, Shiffman S, et al. Two-stage transmucosal medicine delivery system for symptom relief. US Patent 6,358,060. 2002 Mar 19

  66. Niaura R, Sayette MA, Shiffman S, et al. Comparative efficacy of rapid-release nicotine gum vs nicorette in relieving smoking cue-provoked craving [abstract]. Annual Meeting of the Society for Research on Nicotine and Tobacco; 2003 Feb 19–22; New Orleans

  67. Henningfield JE, Stapleton JM, Benowitz NL, et al. Higher levels of nicotine in arterial than in venous blood after cigarette smoking. Drug Alcohol Depend 1993; 33: 23–9

    Article  PubMed  CAS  Google Scholar 

  68. McClain H, Sapeinza F. The role of abuse liability testing in drug control procedures. In: Fischman MW, Mello NK, editors. Testing for abuse liability of drugs in humans: NIDA research monograph no. 92. Rockville (MD): US Department of Health and Human Services, 1989: 21–42

    Google Scholar 

  69. Shiffman S, Gitchell JG, Warner KE, et al. Tobacco harm reduction: conceptual structure and nomenclature for analysis and research. Nicotine Tob Res 2002; 4 Suppl. 2: S113–29

    Article  Google Scholar 

  70. Balfour DJ, Fagerstrom KO. Pharmacology of nicotine and its therapeutic use in smoking cessation and neurodegenerative disorders. Pharmacol Ther 1996; 72: 51–81

    Article  PubMed  CAS  Google Scholar 

  71. Institute of Medicine. Clearing the smoke: assessing the science base for tobacco harm. Washington, DC: National Academy Press, 2001

    Google Scholar 

  72. Bolliger CT, Zellweger JP, Danielsson T, et al. Smoking reduction with oral nicotine inhalers: double blind, randomised clinical trial of efficacy and safety. BMJ 2000; 321: 329–33

    Article  PubMed  CAS  Google Scholar 

  73. Hurt RD, Croghan GA, Wolter TD, et al. Does smoking reduction result in reduction of biomarkers associated with harm: a pilot study using a nicotine inhaler. Nicotine Tob Res 2000; 2: 327–36

    Article  PubMed  CAS  Google Scholar 

  74. Carpenter MJ, Hughes JR, Keely JP. Does reducing smoking change readiness to quit smoking [abstract]. Annual Meeting of the College for Problems on Drug Dependence; 2000 Jun 17–22; San Juan

  75. Ariva™ [online]. Available from URL: http://www.goariva.com [Accessed 2000 Apr 22]

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Acknowledgements

Dr Henningfield was supported by an Innovators Combating Substance Abuse Award from the Robert Wood Johnson Foundation.

Drs Shiffman, Fant, Gitchell, Cone, and Henningfield serve as consultants to GSKCH on an exclusive basis regarding matters relating to smoking cessation. Drs Shiffman, Gitchell, and Henningfield also have an interest in a new nicotine replacement product. Dr Fagerström has worked full time for Pharmacia up to 1998, a manufacturer of nicotine replacement medications, and has since consulted for other manufacturers/marketers of nicotine replacement medications (GSKCH, Novartis, and Ceejay Healthcare). Dr Fagerström also has stock in a company developing nicotine replacement medications.

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Authors and Affiliations

  1. Department of Psychology, Smoking Research Group, University of Pittsburgh, 130 N. Bellefield, Bellefield Prof Bldg Ste 510, Pittsburgh, Pennsylvania, 15260, USA

    Saul Shiffman

  2. Pinney Associates, Pittsburgh, Pennsylvania, USA

    Saul Shiffman

  3. Pinney Associates, Bethesda, Maryland, USA

    Reginald V. Fant, Joseph G. Gitchell, Edward J. Cone & Jack E. Henningfield

  4. Department of Psychiatry and Behavioral Science, The Johns Hopkins University School of Medicine, Baltimore, Maryland, USA

    Jack E. Henningfield

  5. Fagerström Consulting, Smokers Information Centre, Helsingborg, Sweden

    Karl O. Fagerström

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  1. Saul Shiffman
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  2. Reginald V. Fant
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  3. Joseph G. Gitchell
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  4. Edward J. Cone
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  5. Jack E. Henningfield
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  6. Karl O. Fagerström
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Correspondence to Saul Shiffman.

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Shiffman, S., Fant, R.V., Gitchell, J.G. et al. Nicotine delivery systems. Am J Drug Deliv 1, 113–124 (2003). https://doi.org/10.2165/00137696-200301020-00003

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