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Different dissolution conditions affect stability and dissolution profiles of bioequivalent levodopa-containing oral
Johanna Weitzel1, Angelika Wünsch1, Olaf Rose2
1Institute of Pharmaceutical Technology and Biopharmacy, University of Muenster, Corrensstraße, 48, 48149 Muenster, Germany.
International Journal of Pharmaceutics
|November 17, 2022
Summary
Generic Parkinson's medications like levodopa/carbidopa may not perform identically. Dissolution and carbidopa stability varied significantly in different media, questioning the safety of generic substitution.
Area of Science:
- Pharmacology
- Drug Formulation
- Bioavailability Studies
Background:
- Parkinson's disease treatments often involve levodopa/carbidopa combinations.
- Generic drug substitution aims to reduce healthcare costs.
- Standardized bioavailability assessments may not reflect real-world drug performance.
Purpose of the Study:
- To characterize levodopa combination formulations from different manufacturers in biorelevant media.
- To assess the impact of various dissolution media on drug performance.
- To evaluate the stability of active ingredients under different conditions.
Main Methods:
- Dissolution profiling of levodopa/carbidopa and levodopa/carbidopa/entacapone combinations.
- Testing in biorelevant media: tap water, simulated gastric fluid (no pepsin), and whole milk.
- Carbidopa stability testing with and without entacapone, and with vitamin C.
Main Results:
- Significant discrepancies in dissolution profiles were observed between different manufacturers.
- Whole milk caused the most variation in dissolution profiles.
- Carbidopa demonstrated instability in tap water and milk, degrading rapidly, an effect lessened by entacapone.
- Entacapone showed poor solubility in acidic conditions.
- Vitamin C did not protect carbidopa from degradation in this study.
Conclusions:
- Bioequivalent levodopa formulations exhibit variable dissolution based on the media.
- Carbidopa stability is a critical factor impacting drug efficacy.
- Maintaining an acidic environment during administration is crucial.
- Caution is advised for generic substitution of levodopa combinations due to observed variability.
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