Skip to main content

Design and Development of Systemic Oral Mucosal Drug Delivery Systems

  • Chapter
  • First Online:
Oral Mucosal Drug Delivery and Therapy

Abstract

This chapter describes the potential of the oral cavity as a site for the systemic delivery of drugs alongside some of the problems and their solutions. Successful clinical applications are described with examples of the research in this area.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

eBook
USD 16.99
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 109.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 109.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Beckett A, Triggs E (1967) Buccal absorption of basic drugs and its application as an in vivo model of passive drug transfer through lipid membranes. J Pharm Pharmacol 19(Suppl):31S–41S

    PubMed  Google Scholar 

  2. Beckett A, Moffat A (1969) The influence of substitution in phenylacetic acids on their performance in the buccal absorption test. J Pharm Pharmacol 21(S1):139S–143S

    Article  PubMed  Google Scholar 

  3. Veillard MM, Longer MA, Martens TW, Robinson JR (1987) Preliminary studies of oral mucosal delivery of peptide drugs. J Control Release 6(1):123–131

    Article  CAS  Google Scholar 

  4. Rathbone MJ, Purves R, Ghazali F, Ho P (1996) In vivo techniques for studying the oral mucosal absorption characteristics of drugs in animals and humans. Drugs Pharm Sci 74:121–156

    Google Scholar 

  5. Rathbone MJ, Hadgraft J (1991) Absorption of drugs from the human oral cavity. Int J Pharm 74(1):9–24

    Article  CAS  Google Scholar 

  6. Rathbone MJ (1991) Human buccal absorption. I. A method for estimating the transfer kinetics of drugs across the human buccal membrane. Int J Pharm 69(2):103–108

    Article  CAS  Google Scholar 

  7. Rathbone MJ (1991) Human buccal absorption. II. A comparative study of the buccal absorption of some parahydroxybenzoic acid derivatives using the buccal absorption test and a buccal perfusion cell. Int J Pharm 74(2):189–194

    Article  CAS  Google Scholar 

  8. Şenel S, Duchene D, Hıncal A, Capan Y, Ponchel G (1998) In vitro studies on enhancing effect of sodium glycocholate on transbuccal permeation of morphine hydrochloride. J Control Release 51(2):107–113

    PubMed  Google Scholar 

  9. Şenel S, Kremer MJ, KaŞ S, Wertz PW, Hıncal AA, Squier CA (2000) Enhancing effect of chitosan on peptide drug delivery across buccal mucosa. Biomaterials 21(20):2067–2071

    Article  PubMed  Google Scholar 

  10. Patel VF, Liu F, Brown MB (2012) Modeling the oral cavity: in vitro and in vivo evaluations of buccal drug delivery systems. J Control Release 161(3):746–756

    Article  CAS  PubMed  Google Scholar 

  11. Şenel S, Capan Y, Sargon M, Ikinci G, Şolpan D, Güven O, Boddé H, Hincal A (1997) Enhancement of transbuccal permeation of morphine sulfate by sodium glycodeoxycholate in vitro. J Control Release 45(2):153–162

    Article  Google Scholar 

  12. Keely S, Ryan SM, Haddleton DM, Limer A, Mantovani G, Murphy EP, Colgan SP, Brayden DJ (2009) Dexamethasone-pDMAEMA polymeric conjugates reduce inflammatory biomarkers in human intestinal epithelial monolayers. J Control Release 135(1):35–43

    Article  PubMed Central  CAS  PubMed  Google Scholar 

  13. Şenel S, Hıncal AA (2001) Drug permeation enhancement via buccal route: possibilities and limitations. J Control Release 72(1):133–144

    PubMed  Google Scholar 

  14. Williams AC, Barry BW (2004) Penetration enhancers. Adv Drug Deliv Rev 56(5):603–618. doi:10.1016/j.addr.2003.10.025

    Article  CAS  PubMed  Google Scholar 

  15. Nicolazzo JA, Reed BL, Finnin BC (2005) Buccal penetration enhancers—how do they really work? J Control Release 105(1):1–15

    Article  CAS  PubMed  Google Scholar 

  16. Sandri G, Rossi S, Bonferoni MC, Ferrari F, Zambito Y, Colo GD, Caramella C (2005) Buccal penetration enhancement properties of N-trimethyl chitosan: influence of quaternization degree on absorption of a high molecular weight molecule. Int J Pharm 297(1):146–155

    Article  CAS  PubMed  Google Scholar 

  17. Pather SI, Rathbone MJ, Şenel S (2008) Current status and the future of buccal drug delivery systems. Expert Opin Drug Deliv 5(5):1–12

    Article  Google Scholar 

  18. Moscicka-Studzinska A, Kijeńska E, Ciach T (2009) Electroosmotic flow as a result of buccal iontophoresis–buccal mucosa properties. Eur J Pharm Biopharm 72(3):595–599

    Article  CAS  PubMed  Google Scholar 

  19. Ciach T, Moscicka-Studzinska A (2011) Buccal iontophoresis: an opportunity for drug delivery and metabolite monitoring. Drug Discov Today 16(7):361–366

    Article  CAS  PubMed  Google Scholar 

  20. Jacobsen J (2001) Buccal iontophoretic delivery of atenolol· HCl employing a new in vitro three-chamber permeation cell. J Control Release 70(1):83–95

    Article  CAS  PubMed  Google Scholar 

  21. Giannola LI, De Caro V, Giandalia G, Siragusa MG, Campisi G, Florena AM, Ciach T (2007) Diffusion of naltrexone across reconstituted human oral epithelium and histomorphological features. Euro J Pharm Biopharm 65(2):238–246

    Article  CAS  Google Scholar 

  22. Giannola LI, De Caro V, Giandalia G, Siragusa MG, Tripodo C, Florena AM, Campisi G (2007) Release of naltrexone on buccal mucosa: permeation studies, histological aspects and matrix system design. Eur J Pharm Biopharm 67(2):425–433

    Article  CAS  PubMed  Google Scholar 

  23. Moscicka AE, Czarnecka K, Ciach T (2007) IntelliDrug implant for medicine delivery in Alzheimer’s disease treatment. In: Macromolecular symposia, vol 1. Wiley Online Library, New York, pp 134–138

    Google Scholar 

  24. Oh D-H, Chun K-H, Jeon S-O, Kang J-W, Lee S (2011) Enhanced transbuccal salmon calcitonin (sCT) delivery: effect of chemical enhancers and electrical assistance on in vitro sCT buccal permeation. Eur J Pharm Biopharm 79(2):357–363

    Article  CAS  PubMed  Google Scholar 

  25. Scholz OA, Wolff A, Schumacher A, Giannola LI, Campisi G, Ciach T, Velten T (2008) Drug delivery from the oral cavity: focus on a novel mechatronic delivery device. Drug Discov Today 13(5):247–253

    Article  CAS  PubMed  Google Scholar 

  26. Kohnle J, Wolff A (2007) Intelligent drug delivery from the oral cavity. Med Device Technol 18(2):44

    CAS  PubMed  Google Scholar 

  27. Campisi G, Giannola LI, Florena AM, De Caro V, Schumacher A, Göttsche T, Paderni C, Wolff A (2010) Bioavailability in vivo of naltrexone following transbuccal administration by an electronically-controlled intraoral device: a trial on pigs. J Control Release 145(3):214–220

    Article  CAS  PubMed  Google Scholar 

  28. Paderni C, Campisi G, Schumacher A, Göttsche T, Giannola LI, De Caro V, Wolff A (2013) Controlled delivery of naltrexone by an intraoral device: in vivo study on human subjects. Int J Pharm 452(1):128–134

    Article  CAS  PubMed  Google Scholar 

  29. Giannola LI, Paderni C, De Caro V, Florena A, Wolff A, Campisi G (2010) New prospectives in the delivery of galantamine for elderly patients using the IntelliDrug intraoral device: in vivo animal studies. Curr Pharm Des 16(6):653–659

    Article  CAS  PubMed  Google Scholar 

  30. Peppas NA, Buri PA (1985) Surface, interfacial and molecular aspects of polymer bioadhesion on soft tissues. J Control Release 2:257–275

    Article  CAS  Google Scholar 

  31. Ch’Ng HS, Park H, Kelly P, Robinson JR (1985) Bioadhesive polymers as platforms for oral controlled drug delivery II: synthesis and evaluation of some swelling, water-insoluble bioadhesive polymers. J Pharm Sci 74(4):399–405

    Article  PubMed  Google Scholar 

  32. Sanzgiri YD, Topp EM, Benedetti L, Stella VJ (1994) Evaluation of mucoadhesive properties of hyaluronic acid benzyl esters. Int J Pharm 107(2):91–97

    Article  CAS  Google Scholar 

  33. Lehr C-M, Bouwstra JA, Schacht EH, Junginger HE (1992) In vitro evaluation of mucoadhesive properties of chitosan and some other natural polymers. Int J Pharm 78(1):43–48

    Article  CAS  Google Scholar 

  34. Marriott C, Hughes DRL (1990) Mucus physiology and pathology bioadhesion—possibilities and future trends. In: Gurny R, Junginger HE (eds) Wissenschaftliche-Verlagsgesellschaft, Stuttgart, pp 29–43

    Google Scholar 

  35. Salamat-Miller N, Chittchang M, Johnston TP (2005) The use of mucoadhesive polymers in buccal drug delivery. Adv Drug Deliv Rev 57(11):1666–1691

    Article  CAS  PubMed  Google Scholar 

  36. Laffleur F (2014) Mucoadhesive polymers for buccal drug delivery. Drug Dev Ind Pharm 40(5):591–598

    Article  CAS  PubMed  Google Scholar 

  37. Şenel S (2010) Potential applications of chitosan in oral mucosal delivery. J Drug Deliv Sci Technol 20:23–32

    Article  Google Scholar 

  38. Pather I, Şenel S, Rathbone MJ (2008) Oral mucosal drug delivery. In: Rathbone MJ, Hadgraft J, Roberts MS, Lane ME (eds) Modified-release drug delivery technology, vol 1. Informa Healthcare, New York, pp 53–73

    Google Scholar 

  39. Şenel S, Rathbone MJ, Cansiz M, Pather I (2012) Recent developments in buccal and sublingual delivery systems. Expert Opin Drug Deliv 9(6):615–628

    Article  PubMed  Google Scholar 

  40. Davies AN, Dickman A, Reid C, Stevens AM, Zeppetella G (2009) The management of cancer-related breakthrough pain: recommendations of a task group of the science committee of the association for palliative medicine of Great Britain and Ireland. Eur J Pain 13(4):331–338

    Article  PubMed  Google Scholar 

  41. Portenoy RK, Payne D, Jacobsen P (1999) Breakthrough pain: characteristics and impact in patients with cancer pain. Pain 81(1):129–134

    Article  CAS  PubMed  Google Scholar 

  42. Hwang SS, Chang VT, Kasimis B (2003) Cancer breakthrough pain characteristics and responses to treatment at a VA medical center. Pain 101(1):55–64

    Article  PubMed  Google Scholar 

  43. Pather SI, Khankari RK, Siebert JM (2003) OraVescent®: a novel technology for the transmucosal delivery of drugs. In: Rathbone MJ, Hadgraft J, Roberts MS (eds) Modified-release drug delivery technology. Marcel Dekker, New York,

    Google Scholar 

  44. Darwish M, Kirby M, Robertson P Jr, Tracewell W, Jiang JG (2006) Pharmacokinetic properties of fentanyl effervescent buccal tablets: a phase I, open-label, crossover study of single-dose 100, 200, 400, and 800 μg in healthy adult volunteers. Clin Ther 28(5):707–714

    Article  CAS  PubMed  Google Scholar 

  45. Fine PG, Messina J, Xie F, Rathmell J (2010) Long-term safety and tolerability of fentanyl buccal tablet for the treatment of breakthrough pain in opioid-tolerant patients with chronic pain: an 18-month study. J Pain Symptom Manage 40(5):747–760

    Article  CAS  PubMed  Google Scholar 

  46. Palem CR, Kumar Battu S, Maddineni S, Gannu R, Repka MA, Yamsani MR (2013) Oral transmucosal delivery of domperidone from immediate release films produced via hot-melt extrusion technology. Pharm Dev Technol 18(1):186–195

    Article  CAS  PubMed  Google Scholar 

  47. McIntyre J, Robertson S, Norris E, Appleton R, Whitehouse WP, Phillips B, Martland T, Berry K, Collier J, Smith S (2005) Safety and efficacy of buccal midazolam versus rectal diazepam for emergency treatment of seizures in children: a randomised controlled trial. Lancet 366(9481):205–210

    Article  CAS  PubMed  Google Scholar 

  48. Nakken K, Lossius M (2011) Buccal midazolam or rectal diazepam for treatment of residential adult patients with serial seizures or status epilepticus. Acta Neurol Scand 124(2):99–103

    Article  CAS  PubMed  Google Scholar 

  49. Medicinal chewing gum Generex website press release. http://www.drugs.com/clinical_trials/generex-announces-positive-results-metformin-chewing-gum-trial-6349.html. Accessed 24 Dec 2014

  50. Oral-lyn1 Generex http://www.generex.com/index.php/id/270. Accessed 26 April 2014

  51. Modi P, Mihic M, Lewin A (2002) The evolving role of oral insulin in the treatment of diabetes using a novel RapidMist™ system. Diabetes Metab Res Rev 18(S1):S38–S42

    Article  CAS  PubMed  Google Scholar 

  52. Oral-lyn Generex. http://investor.generex.com/releasedetail.cfm?ReleaseID=776114. Accessed 26 April 2014

  53. FDA News Release. http://www.fda.gov/NewsEvents/Newsroom/PressAnnouncements/ucm281013.htm. Accessed 26 April 2014

  54. Intermezzo Purdue Pharma L.P. http://www.intermezzorx.com/hcp/index.aspx. Accessed 26 April 2014

  55. Greenblatt DJ, Harmatz JS, Roth T, Singh NN, Moline ML, Harris SC, Kapil RP (2013) Comparison of pharmacokinetic profiles of zolpidem buffered sublingual tablet and zolpidem oral immediate-release tablet: results from a single-center, single-dose, randomized, open-label crossover study in healthy adults. Clin Ther 35(5):604–611

    Article  CAS  PubMed  Google Scholar 

  56. Utsman RA, Epstein JB, Elad S (2008) Budesonide for local therapy of complex oral mucosal immune-mediated inflammatory diseases: case reports. Oral Surg Oral Med Oral Pathol Oral Radiol Endod 106(1):e11–e17

    Article  Google Scholar 

  57. Dilger K, Halter J, Bertz H, Lopez-Lazaro L, Gratwohl A, Finke J (2009) Pharmacokinetics and pharmacodynamic action of budesonide after buccal administration in healthy subjects and patients with oral chronic graft-versus-host disease. Biol Blood Marrow Transplant 15(3):336–343

    Article  CAS  PubMed  Google Scholar 

  58. Reuters website article2. http://www.reuters.com/article/2011/05/26/idUS50920+26-May-2011+RNS20110526. Accessed 26 April 2014

  59. Nurmikko TJ, Serpell MG, Hoggart B, Toomey PJ, Morlion BJ, Haines D (2007) Sativex successfully treats neuropathic pain characterised by allodynia: a randomised, double-blind, placebo-controlled clinical trial. Pain 133(1):210–220

    Article  CAS  PubMed  Google Scholar 

  60. Striant website. http://www.auxilium.com/product-portfolio/our-products/striant/. Accessed 24 Dec 2014

  61. Reckitt Benkiser website. http://www.rb.com/investors-media/announcements-and-presentations. Accessed 25 July 2014

  62. Lintzeris N, Leung S, Dunlop A, Larance B, White N, Rivas G, Holland R, Degenhardt L, Muhleisen P, Hurley M (2013) A randomised controlled trial of sublingual buprenorphine–naloxone film versus tablets in the management of opioid dependence. Drug Alcohol Depend 131(1):119–126

    Article  CAS  PubMed  Google Scholar 

  63. Gerrits M, de Greef R, Peeters P (2010) Effect of absorption site on the pharmacokinetics of sublingual asenapine in healthy male subjects. Biopharm Drug Dispos 31(5–6):351–357

    CAS  PubMed  Google Scholar 

  64. Berlin I, Jacob N, Coudert M, Perriot J, Schultz L, Rodon N (2011) Adjustment of nicotine replacement therapies according to saliva cotinine concentration: the ADONIS* trial—a randomized study in smokers with medical comorbidities. Addiction 106(4):833–843

    Article  PubMed  Google Scholar 

  65. Ashburn MA, Slevin KA, Messina J, Xie F (2011) The efficacy and safety of fentanyl buccal tablet compared with immediate-release oxycodone for the management of breakthrough pain in opioid-tolerant patients with chronic pain. Anesth Analg 112(3):693–702

    Article  CAS  PubMed  Google Scholar 

  66. Saunders DL, Messina J, Darwish M, Xie F, Leary KJ, Cantilena LR (2012) Assessment of the relative potency of fentanyl buccal tablet to intravenous morphine in healthy volunteers using a thermally induced hyperalgesia pain model. J Clin Pharm 52(6):870–879

    Article  CAS  Google Scholar 

  67. Finn AL, Vasisht N, Stark JG, Gever LN, Tagarro I (2012) Dose proportionality and pharmacokinetics of fentanyl buccal soluble film in healthy subjects. Clin Drug Invest 32(1):63–71.

    Article  CAS  Google Scholar 

  68. Oravig website.http://www.oravig.com. Accessed 20 Dec 2014

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to Michael John Rathbone .

Editor information

Editors and Affiliations

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Controlled Release Society

About this chapter

Cite this chapter

Rathbone, M., Şenel, S., Pather, I. (2015). Design and Development of Systemic Oral Mucosal Drug Delivery Systems. In: Rathbone, M., Senel, S., Pather, I. (eds) Oral Mucosal Drug Delivery and Therapy. Advances in Delivery Science and Technology. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-7558-4_7

Download citation

Publish with us

Policies and ethics