Skip to main content
SpringerLink
Log in

Pramlintide injection drug product robustness studies

  • Published:
AAPS PharmSciTech Aims and scope Submit manuscript

Abstract

The article examines the effects of temperature excursions and actual dose withdrawal on the quality of pramlintide injection, a multidose liquid parenteral formulation. Studies were designed to demonstrate product robustness under conditions that may occur during patient use. Pramlintide %Purity was determined by two high-performance liquid chromatography (HPLC) methods, a reversed-phase (RP-HPLC) and a strong-cation exchange (SCX-HPLC) method. A second RP-HPLC method was used to determine pramlintide potency and the concentration of them-cresol preservative. Antimicrobial preservative effectiveness testing was per USP and European Pharmacopeia (Ph. Eur.). Short-term stability studies were undertaken to probe the effects of the following conditions: 5°C to 40°C and 5°C to −20°C temperature cycling over 10 days; once daily or four-times daily dose withdrawal over 12 or 42 days; and combined 30°C storage and four-times daily dose withdrawal over 42 days. In all cases, pramlintide %Purity and potency values remained essentially unchanged or unchanged relative to controls. Similarly, product appearance, andm-cresol concentration and preservative effectiveness were not significantly affected by the stress conditions used in the 5 studies. Pramlintide injection drug product is extremely robust to challenging stress conditions that may occur during patient use of this multidose product for chronic administration.

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

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Similar content being viewed by others

References

  1. Young A, Pittner R, Gedulin B, Vine W, Rink T. Amylin Regulation of carbohydrate metabolism. Biochem Soc Trans. 1995;23:325–331.

    CAS  PubMed  Google Scholar 

  2. Scherbaum WA. The role of amylin in the physiology of glycemic control. Experimental and Clinical Endocrinol and Diabetes. 1998:106(2):97–102.

    Article  CAS  Google Scholar 

  3. Amiel S. Amylin and diabetes. Lancet. 1993:341:1249–1250.

    Article  CAS  PubMed  Google Scholar 

  4. Janes S, Gaeta L, Beaumont K, Beeley K, Rink T. The selection of pramlintide for clinical evaluation. Diabetes. 1996;45 (Suppl 2): 235A.

    Google Scholar 

  5. Thompson RG, Gottlieb A, Organ K, Kolterman OG. Pramlintide, a human amylin analog reduced post-prandial plasma glucose, insulin and epeptide concentrations in patients with type II diabetes. Diabetic Medicine. 1997;14(7):547–555.

    Article  CAS  PubMed  Google Scholar 

  6. Thompson RG, Peterson J, Gottlieb A, Mullane J. Effects of pramlintide, an analog of human amylin on plasma glucose profiles in patients with IDDM: results of a multi-center trial. Diabetes. 1997;46(4):632–636.

    Article  CAS  PubMed  Google Scholar 

  7. Brower V. Amylin's pramlintide best of bad bunch of diabetes drugs. Nature Biotechnol. 1997;15(10):935.

    Article  CAS  Google Scholar 

  8. Hekman C, Demond W, Dixit T, et al. Isolation and identification of peptide degradation products of heat stressed pramlintide injection. Pharmaceutical Research 1998;15:650–659.

    Article  CAS  PubMed  Google Scholar 

  9. Kenley R, Demond W, L'Italien J, Lokensgard D, Weilersbacher G. Orthogonal HPLC methods for quantitating related substances and degradation products of pramlintide.AAPS PharmSciTech 1(n1) 2000 (http://www.pharmscitech.com|url)

  10. Kenley R, Tracht S, Stepanenko A, Townsend M, L'Italien J. Kinetics of pramlintide degradation in aqueous solution as a function of temperature and p..AAPS PharmSciTech 1(2) 2000 (http://www.pharmscitech.com|url)

  11. International Committee on Harmonization ICH Q5C. “Guideline for Industry: Quality of Biotechnological Products: Stability Testing of Biotechnological/Biological Products”. Section VI.C.1996.

  12. Committee for Proprietary Medicinal Products. European Agency for the Evaluation of Medicinal Products. “Note for Guidance on Inclusion of Antioxidants and Antimicrobial Preservatives in Medicinal Products”. Section 8. 1998.

  13. Committee for Proprietary Medicinal Products. European Agency for the Evaluation of Medicinal Products. “Note for Guidance on Development Pharmaceutics”. Section 3.3.1., 1998.

  14. U.S. Food and Drug Administration Center for Drug Evaluation and Research, Department of Health and Human Services. “Guideline for Submitting Documentation for Packaging for Human Drugs and Biologics”. Section III.B. 1987.

  15. International Committee on Hamonization ICH Q5C “Guideline for Industry: Quality of Biotechnological Products: Stability Testing of Biotechnological Biological Products”. Section VI.E. 1996.

Download references

Author information

Authors and Affiliations

  1. Cabrillo Facility of Magellan Laboratories, Inc., 9250 Trade Place, 92126, San Diego, CA

    Richard A. Kenley & Anna Stepanenko

  2. Amylin Pharmaceuticals, Inc., 9373 Towne Centre Drive, 92121, San Diego, CA

    Fred Bancroft

  3. Baxter Hyland, Glendale, CA

    James L'Italien

  4. ISIS Pharmaceuticals, Inc., Carlsbad, CA

    Michael Townsend

  5. TAP Pharmaceuticals, Inc., Deerfield, IL

    Trupti Dixit

Authors
  1. Richard A. Kenley
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Fred Bancroft
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. James L'Italien
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. Anna Stepanenko
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. Michael Townsend
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. Trupti Dixit
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Richard A. Kenley.

Rights and permissions

Reprints and permissions

About this article

Check for updates. Verify currency and authenticity via CrossMark

Cite this article

Kenley, R.A., Bancroft, F., L'Italien, J. et al. Pramlintide injection drug product robustness studies. AAPS PharmSciTech 1, 8 (2000). https://doi.org/10.1208/pt010208

Download citation

  • Received:

  • Accepted:

  • Published:

  • DOI: https://doi.org/10.1208/pt010208

Keywords

Search

Navigation