Different dissolution conditions affect stability and dissolution profiles of bioequivalent levodopa-containing oral dosage forms

Parkinson's disease is frequently treated with combinations of levodopa/carbidopa and, at the occurrence of motor fluctuations, levodopa/carbidopa/entacapone. For these (and other) medications, using generic versions can reduce costs. To show that generic drugs are equivalent to the originator drug, regulations usually refer to the bioavailability of active ingredients, which is influenced by the selected dosage form and the chosen excipients. However, while registration trials administer drugs under standardized conditions, these conditions often do not reflect the conditions of patients' daily intake. Thus, this study aimed to characterize levodopa combinations from different manufacturers in biorelevant media.Dissolution profiles of bioequivalent levodopa/carbidopa combinations and levodopa/carbidopa/entacapone combinations were tested in different media, such as tap water, gastric fluid without pepsin and whole milk. Results showed distinct discrepancies in the drugs' dissolution profiles between manufactures. Using whole milk as a dissolution medium led to the most differing dissolution profiles. Furthermore, carbidopa was unstable in tap water and milk, and it rapidly degraded. This effect was less pronounced if entacapone was present. In contrast to reports in the literature, stability testing did not show that vitamin C helps to protect against carbidopa degradation. Entacapone hardly dissolved in an acidic environment.This study found that dissolution of bioequivalent levodopa formulations varied with changing media. Further, the stability of carbidopa was found to be critical. As an implication, an acidic environment must be ensured when these drugs are applied, and generic exchange of levodopa combinations should be considered only with great caution.

Automated summary

This study tested the dissolution profiles of bioequivalent levodopa combinations and found that there were significant differences between manufacturers. Carbidopa was found to be unstable in tap water and milk, while entacapone hardly dissolved in an acidic environment. It is important to ensure an acidic environment when using these drugs, and caution should be taken when considering the substitution of generic levodopa combinations.