Quality and behavior of glimepiride generics versus amaryl under stressed conditions.
BACKGROUND
The use of generic versions of drugs, such as those for glimepiride [Amaryl, Amarel, Solosa (sanofi-aventis, Paris, France)], a third-generation sulfonylurea, can reduce healthcare costs. However, the quality and performance of these generics should be carefully evaluated.


METHODS
We compared the quality and behavior of 23 marketed generic forms with Amaryl (all 2 mg) under stressed conditions. Deblistered samples were stored at 60 degrees C for 21 days in order to mimic temperature-stressed conditions. Samples were analyzed at Days 0, 7, and 21 for content of active compound, levels of impurities, levels of residual solvent (Day 0 only), and dissolution profile, and results were compared against Amaryl specifications.


RESULTS
Levels of the degradation product GS [corrected] were < or = 1% in all products at Day 0; however, GS levels [corrected] increased to above Amaryl specifications [corrected] in two generics at Day 7 (Dolcyl and GLA-DM) [corrected] and in four generics at Day 21 [Dolcyl, GLA-DM, glimepiride (Hanni), and glimepirida (Esterlina)] (Fig. 2) [corrected] Total levels of other impurities and levels of residual solvents were above Amaryl specifications (<or=1.0% and >1,400 ppm, respectively) in two generics at Day 0. At Day 0, the dissolution of 12 generics (52%) failed to meet Amaryl specifications (>or=85% dissolved in 15 min); this trend was confirmed at Day 21. Overall, 74% (17 of 23) of the generics were not of equivalent quality or performance compared with Amaryl.


CONCLUSIONS
This study indicates that a relevant percentage of glimepiride generics may offer reduced quality and performance when compared with the original drug.
Attorrese
Giuseppe
G
Sanofi-aventis, Scoppito, Italy.
Massi-Benedetti
Massimo
M
D004353:Drug Evaluation, Preclinical; D004355:Drug Stability; D004356:Drug Storage; D064420:Drug-Related Side Effects and Adverse Reactions; D016568:Drugs, Generic / Q000032:analysis* / Q000592:standards; D007004:Hypoglycemic Agents / Q000032:analysis* / Q000592:standards; D013453:Sulfonylurea Compounds / Q000032:analysis* / Q000592:standards; D013696:Temperature
D016568:Drugs, Generic; D007004:Hypoglycemic Agents; D013453:Sulfonylurea Compounds; C057619:glimepiride