Quality and stability of ramipril generics/copies versus reference ramipril (Tritace): a 3-month stability comparative study.

OBJECTIVE: This study aimed to evaluate the quality and stability over time of marketed ramipril generics/copies, in terms of Sanofi-Aventis specifications, relative to that of the reference ramipril product Tritace.

METHODS: The quality and dissolution profiles of 22 marketed generic/copy tablet formulations of ramipril (2.5 mg) were compared with the reference ramipril tablet (2.5 mg; Tritace). Samples were analysed for levels of ramipril and impurities (as determined by the level of the major metabolite ramipril-diketopiperazine) before and after storage under temperature-stressed conditions (40 degrees C and 75% relative humidity) for 1.5 and 3 months. Dissolution analyses were performed before and after 3 months' temperature-stressed storage. All analytical results were compared with Sanofi-Aventis specifications for the manufacture of the reference ramipril product. One batch per generic/copy drug was analysed.

RESULTS: In terms of the level of ramipril, 24% (4/17) of generics/copies failed to meet reference ramipril specifications (90-105% of label claim) at baseline, increasing to 47% (8/17) after 3 months under stressed conditions. At baseline, the dissolution profiles of 24% (5/21) of generics/copies failed to meet the reference ramipril product specifications (>or=80% dissolved in 30 minutes), with the failure rate increasing to 57% (12/21) after storage for 3 months. Total levels of impurities were above reference ramipril product specifications (<or=5.0%) in 32% (7/22) of generics/copies at baseline, increasing to 68% (15/22) at 3 months. Overall, only 24% (5/21) of the generics/copies were of equivalent quality and showed similar dissolution profiles to that of the reference ramipril product.

CONCLUSIONS: A significant percentage of ramipril generics/copies evaluated showed reduced quality, stability and solubility compared with the reference ramipril product (Tritace), thereby confirming the need for vigilance regarding the evaluation of generics/copies.