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Oral Delivery (Focus Group – OrD)

Nitrosamine Mitigation: A) Development of Direct Compressible Extended-Release (ER) Metformin HCl Tablets

Anne Fuller – Senior Manager, Global Technical Operations, Colorcon; Kevin Hughes – Director, Colorcon
Introduction:

Metformin hydrochloride (HCl) is the most prescribed drug for lowering blood glucose levels. Since 2020, the FDA has recommended voluntary recalls of multiple of its extended-release (ER) drug products due to nitrosamine (i.e., NDMA) levels above acceptable limits.

Metformin HCl is typically formulated using wet granulation due to its poor flow, which is a nitrosamine-enabling unit operation (1). Therefore, this study aims to develop a robust direct compressible (DC) ER tablet using non-DC grade active pharmaceutical ingredient (API) via determining the impact of polymer concentration and filler type. A formulation with granulated API (i.e., DC grade) was used as control.

Learning Objectives:

  • Understand the process of developing robust metformin HCl DC ER formulation, reducing risk of nitrosamine formation
  • Evaluate the impact of API grade, polymer concentration, and filler grade on metformin HCl tablets.