Development of the exubera® insulin pulmonary delivery system

Mucosal Delivery of Biopharmaceuticals: Biology, Challenges and Strategies

Volumn 9781461495246, Issue , 2014, Pages 461-481

  Stevenson, Cynthia L ^a   Bennett, David B ^a  

^a Independent Pharmaceuticals Consultant   (United States)

Author keywords

Clinical trial; Efficacy; Formulation development; Inhaler; Insulin; Pharmacokinetics; Pulmonary delivery; Safety

Indexed keywords

EID: 84930024673     PISSN: None     EISSN: None     Source Type: Book    
DOI: 10.1007/978-1-4614-9524-6_21     Document Type: Chapter

References (50)

1. Narayan KMW, Boyle JP, Thompson TJ, Sorensen SW, Williamson DF. Lifetime risk for developing diabetes mellitus in the United States. JAMA. 2003;290:1884-90.
2. Home PD, Boulton AJM, Jimenez J, Landgraf R, Osterbrink B, Christiansen JS. Issues relating to the early or earlier use of insulin in type 2 diabetes. Pract Diabetes Int. 2003;20:63-71.
3. American Diabetes Association (ADA). Test of glycemia in diabetes. Diabetes Care. 2002;25:S97-S9.
4. Rosenstock J, for the Exubera® Phase III Study Group. Mealtime rapid-Acting inhale insulin (Exubera®) improves glycemic control in patients with type 2 diabetes failing combination oral agents: a 3-month, randomized, comparative trial. Diabetes. 2002;51:A132.
5. Zambanini A, Newson RB, Maisey M, Feher MD. Injection related anxiety in insulin-Treated diabetes. Diabetes Res Clin Pract. 1999;46:239-46.
6. Home PD. Intensive insulin therapy in clinical practice. Diabetologia. 1997;40:S83-S7.
7. CefaluWT. Rationale for and strategies to achieve glycemic control. In: Leahy JL, CefaluWT, editors. Insulin therapy. NewYork: Marcel Dekker; 2002. pp. 1-11.
8. Patton JS. Mechanisms of macromolecule absorption by the lungs. Adv Drug Del Rev. 1996;19:3-36.
9. Smith SJ, Bernstein JA. In: Hickey AJ, editor. Inhalation aerosols: physical and biological basis for therapy. NewYork: Marcel Dekker; 1996. pp. 233-69.
10. Patton JS, Bukar J, Nagarajan S. Inhaled insulin. Adv Drug Del Rev. 1999;35:235-47.
11. Patton JS, Bukar JG, Eldon MA. Clinical pharmacokinetics and pharmacodynamics of inhaled insulin. Clin Pharmacokinet. 2004;43:781-801.
12. Patton JS, Platz RM. Routes of delivery: case studies. Pulmonary delivery of peptides and proteins for systemic action. Adv Drug Del Rev. 1992;8:176-96.
13. White S, Bennett DB, Cheu S, Conley PW, Guzek DB, Gray S, Howard J, Malcolmson R, Parker JM, Roberts P, Schumacher JD, Sadrzadeh N, Seshadri S, Sluggett GW, Stevenson CL, Harper NJ. EXUBERA®: pharmaceutical development of a novel product for pulmonary delivery of insulin. Diabetes Technol Ther. 2005;7:896-906.
14. Harper NJ, Gray S, de Groot J, Parker JM, Sadrzadeh N, Schuler C, Schumacher JD, Seshadri S, SmithAE, Steeno GS, Stevenson CL, Taniere R, Wang M, Bennett DB. Design and performance of the exubera pulmonary insulin delivery system. Diabetes Technol Ther. 2007;9:16-27.
15. Skyler JS, for the Exubera® Phase III Study Group. Efficacy and safety of inhaled insulin (Exubera®) compared to subcutaneous insulin therapy in an intensive insulin regimen in patients with type 1 diabetes: results of a 6-month, randomized, comparative trial. Diabetes. 2002;51:A134.
16. Gelfand RA, Schwartz S, Horton M, Law CG, Pun EF. Pharmacological reproducibility of inhaled human insulin pre-meal dosing in patients with type 2 diabetes mellitus (NIDDM). Diabetes. 1998;47:0388.
17. Balanger A, for the Exubera® Phase III Study Group. Efficacy and safety of inhaled insulin (Exubera®) compared to subcutaneous insulin therapy in an intensive insulin regimen in patients with type 2 diabetes: results of a 6-month, randomized, comparative trial. Diabetologia. 2002;45:A260.
18. Gelfand RA, Schwartz SL, Horton M, Law CG, Pun EF. Pharmacological reproducibility of inhaled human insulin dosed pre-meal in patients with type 2 diabetes mellitus. Diabetes. 2002;51:A202.
19. QuattrinT, BelangerA, BohannonNJV, Schwartz SL. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 1 diabetes. Diabetes Care. 2004;27:2622-27.
20. Hollander PA, Blonde L, Rowe R, MehtaAE, Milburn JL, Hershon KS, Chaisson JL, Levin SR. Efficacy and safety of inhaled insulin in patients with type 2 diabetes: a 6-month, randomized, comparative trial. Diabetes Care. 2004;27:2356-62.
21. Ashurst I, Malton A, Prime D, Sumby S. Latest advances in the development of dry powder inhalers. Pharm Sci Technol Today. 2000;3:246-56.
22. Pikal MJ, Rigsbee DR. Dynamics of pharmaceutical amorphous solids: the study of enthalpy relaxation by isothermal microcalorimetry. Pharm Res. 1997;14:1379-87.
23. Hancock BC, Parks M. What is the true solubility advantage for amorphous pharmaceuticals?. Pharm Res. 2000;17:397-404.
24. Hancock BC, Shamblin SL, Zografi G. Molecular mobility of amorphous pharmaceutical solids below their glass transition temperatures. Pharm Res. 1995;12:799-806.
25. Franks F, Hatley RHM, Mathias SF. Materials science and the production of shelf-stable biologicals. Pharm Technol Int. 1991;3:24-34.
26. Lechuga-Ballesteros D, Kuo MC, Liang Y, Malcolmson R, Miller DP, Sekulic S, Seshadri S, Stults CLM, Tan T, Joshi V, Zhen C, Williams L, Bennett DB the physical stability of insulin powder for inhalation. AAPS J. 2004;6:R6137.
27. Kajiwara K, Franks F, Echlin P, Greer AL. Structural and dynamic properties of crystalline and amorphous phases in raffinose-water mixtures. Pharm Res. 1999;16:1441-8.
28. Lechuga-Ballesteros D, MillerDP, Zhang J. Residualwater in amorphous solids: measurements and effects on stability. In: Levine H, ed. Progression amorphous food and pharmaceutical systems. London: The Royal Society of Chemistry; 2002.
29. Duddu SP, Zhang G, Dal Monte PR the relationship between protein aggregation and molecular mobility below the glass transition temperature of lyophilized formulations containing a monoclonal antibody. Pharm Res. 1997;14:596-600.
30. Hancock BC, Zografi G the relationship between glass transition temperature and the water content of amorphous pharmaceutical solids. Pharm Res. 1994;11:471-7.
31. Suen C, Bennett DB, Sadrzadeh N, Seshadri S, Stevenson CL, Tan MM, Wang ML, Kelly KE. Solution and solid state structural stability of insulin. AAPS J. 2004;6:M1261.
32. Pittman I, Tager HS. A spectroscopic investigation of the conformational dynamics of insulin in solution. Biochemistry. 1995;34:10578-90.
33. Dong A, Caughey WS. Infrared methods for study of hemoglobin reactions and structures. Methods Enzymol. 1994;232:139-75.
34. Sadrzadeh N, Wang ML, Yu M, Antonino L, Stevenson CL, Bennett DB, Kelly ME the chemical stability of spray dried insulin powder for inhalation. AAPS J. 2004;6:M1261.
35. Sadrzadeh N, Miller DP, Lechuga-Ballesteros D, Harper N, Stevenson CL, Bennett DB. Solidstate stability of spray-dried insulin powder for inhalation: chemical kinetics and structural relaxation modeling of exubera above and below the glass transition temperature. J Pharm Sci. 2010;99:3698-710.
36. Malcolmson R, De Moor CP, Miller DP, Liang Y, Zhen C, Kim Y, Merchant J, Bennett D, Mazumder MK, Saracovan I, Sekulic S. Physical properties of bulk insulin powder for inhalation. AAPS J. 2004;6:R6169.
37. Stahl K, Claesson M, Lilliehorn P, Linden H, Backstrom K the effect of process variables on the degradation and physical properties of spray dried insulin intended for inhalation. Int J Pharm. 2002;233:227-37.
38. Vehring R, Tep V, Foss WR. Novel experimental method indicates proteins and peptides are protected from high gas temperatures during spray drying. AAPS PharmSci. 2003;5:M1247.
39. Schuler C, Mao Z, Cameron J. Nektar's dry-powder durable pulmonary drug delivery system: principles of operation. Proceedings of the 31st International Symposium on Controlled Release of Bioactive Materials, Hawaii; 2004.
40. BakshiA, PaboojianA, Rasmussen D, Tuttle D, Snyder H, ClarkA, SmithA, Schuler C. Inhale's dry-powder pulmonary drug delivery system: challenges to current modeling of gas-solid flows. 3rd ASME/JSME Fluids Engineering Conference, San Francisco, CA; 1999.
41. Gray S, Parker J, deGroot J, Ozawa L, Chwa T, Harper N. Performance robustness characteristics of insulin powder for inhalation using a pneumatic inhalation device. Drug Delivery to the Lungs 15, London, UK; 2004.
42. Byron PB. Prediction of drug residence times in regions of the human respiratory tract following aerosol inhalation. J Pharm Sci. 1986;75:433-8.
43. Exubera Product Label, www.accessdata.fda.gov/drugsatfda-docs/label/2008/021868S016S 017lbl.pdf.
44. Kaptiza C, HeiseT, PfutznerA, Steiner S, Heiniemann L, Kave K. Dose-response characteristics for a new pulmonary insulin formulation and inhaler. Diabetologia. 2000;40(Supp 1):A46.
45. FDA Advisory Committee Meeting, September 5, 2005 slides, http://www.fda.gove/ohrms/ dockets/ac/o5/slides/2004-4169S1-00-slide-Index.htm.
46. Exubera Briefing Document, http://www.fda.gov/ohrms/dockets/ac/05/briefing/2005-4169B1-01-01-Pfizer-Exubera.pdf
47. Skyler JS, Jovanovic L, Klioze S, Reis j, Dugan W. Two-year safety and efficacy of inhaled human insulin (Exubera) in adult patients with type 1 diabetes. Diabetes Care. 2007;30:579-85.
48. Quattrin T, Belanger A, Bohannon NJ, Schwartz SL. Efficacy and safety of inhaled insulin (Exubera) compared with subcutaneous insulin therapy in patients with type 1 diabetes results of a 6-month, randomized, comparative trial. Diabetes Care. 2004;27:2622-27.
49. http://clinicaltrials.gov/show/NCT00734591.
50. Heinemann L the failure of exubera: are we beating a dead horse?. J Diabetes Sci Technol. 2008;2:518-29.