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AAPS PharmSciTech

, Volume 14, Issue 1, pp 312–320 | Cite as

Stability Enhancement of Drug Layered Pellets in a Fixed Dose Combination Tablet

  • Matthew D. BurkeEmail author
  • Xiaorong He
  • Chris Cook
  • Greg A. Petrov
  • Susan Long
  • Mark D. Coffin
Research Article

Abstract

The purpose of this research was to develop a stable fixed dose combination tablet for a model DPP-IV inhibitor and metformin hydrochloride. The dipeptidyl peptidase IV (DPP-IV) inhibitor was particularly challenging to formulate due to its significant chemical instability and moisture sensitivity. Various formulation strategies were investigated and placed on accelerated stability to determine the lead approach and critical quality attributes. The lead formulation investigated was a drug layered pellet containing the DPP-IV inhibitor, which was further coated with various seal coats and moisture barriers, then compressed into a tablet with compression aids and granulated metformin hydrochloride. The investigations revealed that the drug layered pellets compressed into a fixed dose combination tablet yielded a unique stability enhancement. The stability was highly dependent on the final tablet water content and could be further improved by the addition of moisture barrier coatings. A fundamental understanding of the key critical quality attributes for the fixed dose combination product containing a DPP-IV inhibitor and metformin hydrochloride as an oral solid dosage form were established. This research identified a formulation approach to enable a successful commercial product to be developed.

KEY WORDS

DPP-IV drug layered pellets hydrolysis moisture barrier stability 

Abbreviations

GI

Gastrointestinal

AMB

Aqueous moisture barrier

DPP-IV

Dipeptidyl peptidase IV

GLP-1

Glucagon-like peptide-1

PVA

Partially hydrolyzed polyvinyl alcohol

HPMC

Hypromellose (hydroxypropylmethylcellulose)

Notes

ACKNOWLEDGMENTS

The authors would like to greatly acknowledge the following people for their ideas, dedication, and hard work that supported this project: Joel Sutton, David Tainsh, Robin Currie, Faith Van Horn, Dustin Melton, Karen Crews, Kaitlin Fague, Ken Ackerman, and Bettina Cremer.

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Copyright information

© American Association of Pharmaceutical Scientists 2013

Authors and Affiliations

  • Matthew D. Burke
    • 1
    Email author
  • Xiaorong He
    • 2
  • Chris Cook
    • 3
  • Greg A. Petrov
    • 3
  • Susan Long
    • 3
  • Mark D. Coffin
    • 3
  1. 1.GlaxoSmithKline R&DHarlowUK
  2. 2.Boehringer Ingelheim Pharmaceuticals R&DRidgefieldUSA
  3. 3.GlaxoSmithKline R&DResearch Triangle ParkUSA

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