Advertisement

The RapidMist™ System for Buccal Delivery of Insulin

Chapter

Abstract

Multiple insulin injections are often required in patients with diabetes mellitus in order to achieve optimal glycemic control. This may reduce patient compliance and increase the risk of long-term microvascular complications in patients. To improve patient compliance, research efforts are focused towards development of needle-free method for insulin delivery. Though a number of different delivery systems and routes have been evaluated for insulin delivery, oral insulin spray formulation offers a number of advantages over others. Oral-lyn™, an oral insulin spray formulation, has been developed by Generex Biotechnology. This delivery system is convenient for patients and can be self-administered using RapidMist™ technology. Insulin is sprayed via the RapidMist™ device into the mouth via an aerosolized spray. Tasteless mist of recombinant human insulin is thus administered to the buccal mucosa. Human studies revealed that absorption of insulin from the formulation is in direct proportion to the amount administered. Insulin delivered via RapidMist™ technology shows a faster onset of action and a shorter duration of action when compared to regular insulin given subcutaneously. Also discussed in this chapter is the safety profile, mechanism of action, and findings of various studies performed on RapidMist™ system.

Keywords

RapidMist™ Oral-lyn™ Buccal insulin Prandial insulin Type 1 diabetes Type 2 diabetes 

References

  1. 1.
    Wild S, Roglic G, Green A, Sicree R, King H. Global prevalence of diabetes: estimates for the year 2000 and projections for 2030. Diabetes Care. 2004;27(5):1047–53.PubMedCrossRefGoogle Scholar
  2. 2.
    Varshosaz J. Insulin delivery system for controlling diabetes. Recent Pat Endocr Metab Immune Drug Discov. 2007;1(1):25–40.CrossRefGoogle Scholar
  3. 3.
    Kumria R, Goomber G. Emerging trends in insulin delivery: buccal route. J Diabetol. 2011;2(1):1–9.CrossRefGoogle Scholar
  4. 4.
    Turner R, Cull C, Holman R. United Kingdom Prospective Diabetes Study 17: a 9-year update of a randomized, controlled trial on the effect of improved metabolic control on complications in non-insulin-dependent diabetes mellitus. Ann Intern Med. 1996;124(1 Pt 2):136–45.PubMedCrossRefGoogle Scholar
  5. 5.
    Bernstein G. Delivery of insulin to the buccal mucosa utilizing the RapidMist system. Expert Opin Drug Deliv. 2008;5(9):1047–55.PubMedCrossRefGoogle Scholar
  6. 6.
    Lee VH. Enzymatic barriers to peptide and protein absorption. Crit Rev Ther Drug Carrier Syst. 1988;5(2):69–97.PubMedGoogle Scholar
  7. 7.
    Heinemann L, Jacques Y. Oral insulin and buccal insulin: a critical reappraisal. J Diabetes Sci Technol. 2009;3(3):568–84.PubMedCentralPubMedCrossRefGoogle Scholar
  8. 8.
    Chidambaram N, Srivatsava AK. Buccal drug delivery systems. Drug Dev Ind Pharm. 1995;21(9):1009–36.CrossRefGoogle Scholar
  9. 9.
    al-Waili NS. Sublingual human insulin for hyperglycaemia in type I diabetes. J Pak Med Assoc. 1999;49(7):167–9.PubMedGoogle Scholar
  10. 10.
    Veuillez F, Kalia YN, Jacques Y, Deshusses J, Buri P. Factors and strategies for improving buccal absorption of peptides. Eur J Pharm Biopharm. 2001;51(2):93–109.PubMedCrossRefGoogle Scholar
  11. 11.
    Rossi S, Sandri G, Caramella CM. Buccal drug delivery: A challenge already won? Drug Discov Today Technol. 2005;2(1):59–65.CrossRefGoogle Scholar
  12. 12.
    Oh CK, Ritschel WA. Biopharmaceutic aspects of buccal absorption of insulin. Methods Find Exp Clin Pharmacol. 1990;12(3):205–12.PubMedGoogle Scholar
  13. 13.
    Oh CK, Ritschel WA. Absorption characteristics of insulin through the buccal mucosa. Methods Find Exp Clin Pharmacol. 1990;12(4):275–9.PubMedGoogle Scholar
  14. 14.
    Generex Biotechnology Corp. Data on File, 2008.Google Scholar
  15. 15.
    Modi P, Mihic M, Lewin A. The evolving role of oral insulin in the treatment of diabetes using a novel RapidMist System. Diabetes Metab Res Rev. 2002;18(Suppl 1):S38–42.Google Scholar
  16. 16.
    The Diabetes Control and Complications Trial Research Group. The effect of intensive treatment of diabetes on the development and progression of long-term complications in insulin-dependent diabetes mellitus. The Diabetes Control and Complications Trial Research Group. N Engl J Med. 1993;329(14):977–86.CrossRefGoogle Scholar
  17. 17.
    UK Prospective Diabetes Study (UKPDS) Group. Intensive blood-glucose control with sulphonylureas or insulin compared with conventional treatment and risk of complications in patients with type 2 diabetes (UKPDS 33). UK Prospective Diabetes Study (UKPDS) Group. Lancet. 1998;352(9131):837–53.CrossRefGoogle Scholar
  18. 18.
    International Diabetes Federation Guideline Development Committee. Guideline for Management of Postmeal Glucose. Brussels: International Diabetes Federation; 2007.Google Scholar
  19. 19.
    Berger M, Cuppers HJ, Hegner H, Jorgens V, Berchtold P. Absorption kinetics and biologic effects of subcutaneously injected insulin preparations. Diabetes Care. 1982;5(2):77–91.PubMedCrossRefGoogle Scholar
  20. 20.
    Binder C, Lauritzen T, Faber O, Pramming S. Insulin pharmacokinetics. Diabetes Care. 1984;7(2):188–99.PubMedCrossRefGoogle Scholar
  21. 21.
    Patton JS, Bukar J, Nagarajan S. Inhaled insulin. Adv Drug Deliv Rev. 1999;35(2–3):235–47.PubMedCrossRefGoogle Scholar
  22. 22.
    Galloway JA, Spradlin CT, Nelson RL, Wentworth SM, Davidson JA, Swarner JL. Factors influencing the absorption, serum insulin concentration, and blood glucose responses after injections of regular insulin and various insulin mixtures. Diabetes Care. 1981;4(3):366–76.PubMedCrossRefGoogle Scholar
  23. 23.
    Almér LO, Wollmer P, Jonson B, Troedsson Almér A. Insulin inhalation with absorption enhancer at meal-times results in almost normal postprandial insulin profiles. Clin Physiol Funct Imaging. 2002;22(3):218–21.PubMedCrossRefGoogle Scholar
  24. 24.
    Cernea S, Kidron M, Wohlgelernter J, Modi P, Raz I. Comparison of pharmacokinetic and pharmacodynamic properties of single-dose oral insulin spray and subcutaneous insulin injection in healthy subjects using the euglycemic clamp technique. Clin Ther. 2004;26(12):2084–91.PubMedCrossRefGoogle Scholar
  25. 25.
    Cernea S, Kidron M, Wohlgelernter J, Modi P, Raz I. Dose-response relationship of oral insulin spray in healthy subjects. Diabetes Care. 2005;28(6):1353–7.PubMedCrossRefGoogle Scholar
  26. 26.
    Pozzilli P, Manfrini S, Costanza F, Coppolino G, Cavallo MG, Fioriti E, Modi P. Biokinetics of buccal spray insulin in patients with type 1 diabetes. Metabolism. 2005;54(7):930–4.PubMedCrossRefGoogle Scholar
  27. 27.
    Guevara-Aguirre J, Guevara-Aguirre M, Saavedra J, Bernstein G, Rosenbloom AL. Comparison of oral insulin spray and subcutaneous regular insulin at mealtime in type 1 diabetes. Diabetes Technol Ther. 2007;9(4):372–6.PubMedCrossRefGoogle Scholar
  28. 28.
    Guevara-Aguirre J, Guevara-Aguirre M, Saavedra J, Bernstein G. 6-month safety and efficacy of lunch-time oral insulin in juvenile type-1 DM subjects receiving basal glargine insulin and pre-breakfast and pre-dinner S.C. regular insulin (abstract), Endocrine Society 89th Annual Meeting, 2007.Google Scholar
  29. 29.
    Guevara-Aguirre J, Guevara-Aguirre M, Saavedra J. A comparison of metabolic control of preprandial S.C. regular insulin versus prandial split doses of an oral insulin (Generex Oral-lyn) in well controlled type 1 diabetes mellitus subjects maintained on twice daily NPH insulin (abstract), Endocrine Society 89th Annual Meeting, 2007.Google Scholar
  30. 30.
    Cernea S, Kidron M, Wohlgelernter J, Raz I. Dose-response relationship of an oral insulin spray in six patients with type 1 diabetes: a single-center, randomized, single-blind, 5-way crossover study. Clin Ther. 2005;27(10):1562–70.PubMedCrossRefGoogle Scholar
  31. 31.
    Guevara-Aguirre J, Guevara M, Saavedra J, Mihic M, Modi P. Beneficial effects of addition of oral spray insulin (Oralin) on insulin secretion and metabolic control in subjects with type 2 diabetes mellitus suboptimally controlled on oral hypoglycemic agents. Diabetes Technol Ther. 2004;6(1):1–8.PubMedCrossRefGoogle Scholar
  32. 32.
    Guevara-Aguirre J, Guevara M, Saavedra J, Mihic M, Modi P. Oral spray insulin in treatment of type 2 diabetes: a comparison of efficacy of the oral spray insulin (Oralin) with subcutaneous (SC) insulin injection, a proof of concept study. Diabetes Metab Res Rev. 2004;20(6):472–8.PubMedCrossRefGoogle Scholar
  33. 33.
    Palermo A, Napoli N, Manfrini S, Lauria A, Strollo R, Pozzilli P. Buccal spray insulin in subjects with impaired glucose tolerance: the prevoral study. Diabetes Obes Metab. 2011;13(1):42–6.PubMedCrossRefGoogle Scholar
  34. 34.
    Heinemann L. Variability of insulin absorption and insulin action. Diabetes Technol Ther. 2002;4(5):673–82.PubMedCrossRefGoogle Scholar
  35. 35.
    Generex Biotechnology Corp. Active Comparator Study of Generex Oral-lyn™ Spray and Injected Human Insulin, ClinicalTrials.gov Identifier: NCT00668850, 2008.Google Scholar

Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  1. 1.Mehr Chand Polytechnic CollegeJalandharIndia
  2. 2.Swift School of PharmacyRajpuraIndia

Personalised recommendations