Evaluation of impurities and dissolution profiles of illegal antimicrobial drugs encountered in Belgium

Abstract

Substandard and falsified (SF) antimicrobials are gaining popularity in both developing and developed countries, posing a growing threat to public health. In general, the evaluation of SF antimicrobial drugs mainly focuses on the identification and quantification of the pharmaceutical active ingredients, ignoring other parameters of drug quality control. This study performed an in‐depth characterization and hazard identification of suspected SF antimicrobial medicinal products encountered in Belgium. In this comprehensive evaluation, impurity tests and dissolution studies were carried out. The dissolution profiles of illegal SF antimicrobials were mathematically compared to their genuine counterparts using the f1 and f2‐factor. The results indicated that 17 out of 57 illegal samples contained higher than permitted amounts of impurities and clearly demonstrated low equivalences of dissolution profiles between SF antimicrobials and genuine products. The variations between tablets at the different time points of the dissolution curves were also higher for the SF medicines. Moreover, 11 out of 19 illegal samples failed to meet the dissolution criteria prescribed by the United States Pharmacopeia. As impurities may induce adverse reactions and improper dissolution patterns may be the cause of insufficient drug efficacy, aggravation of illness and even promotion of antimicrobial resistance can be expected.

Uncovering the Quality Deficiencies with Potentially Harmful Effects in Substandard and Falsified PDE-5 Inhibitors Seized by Belgian Controlling Agencies

“…Although 15 samples were compliant for the performed analysis, it cannot be excluded that they might pose additional chemical risks. This can be due to the possibility that they may contain higher than tolerated levels of API-related impurities, metals and metalloids or even have dissolution profiles with low equivalence, as often seen with substandard and falsified medicines [57,58] or substandard medicines [59]. The latter can then increase the temptation for the patient to consume a second dose, hence increasing the risks again.…”