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AAPS PharmSciTech. 2013 Mar;14(1):312-20. doi: 10.1208/s12249-012-9911-3. Epub 2013 Jan 15.

Stability enhancement of drug layered pellets in a fixed dose combination tablet.

Author information

1
GlaxoSmithKline R&D, New Frontiers Science Park, Third Avenue, Harlow, Essex, UK, CM19 5AW. matthew.d.burke@gsk.com

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.

PMID:
23319298
PMCID:
PMC3581657
DOI:
10.1208/s12249-012-9911-3
[Indexed for MEDLINE]
Free PMC Article
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