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Influence of tablet dissolution on furosemide bioavailability: a bioequivalence study
P J McNamara1, T S Foster, G A Digenis
1College of Pharmacy, University of Kentucky, Lexington 40506.
Pharmaceutical Research
|April 1, 1987
Summary
This study evaluated furosemide (40 mg) bioequivalence. In vitro dissolution at pH 5.6 correlated with in vivo urine excretion, suggesting it as a suitable test for furosemide products.
Area of Science:
- Pharmacokinetics and Drug Metabolism
- Pharmaceutical Sciences
- Bioequivalence Studies
Background:
- Establishing the relationship between in vitro dissolution and in vivo bioavailability is crucial for pharmaceutical product development.
- Furosemide, a potent diuretic, requires careful formulation to ensure consistent therapeutic effects.
- Bioequivalence studies are essential for regulatory approval and ensuring therapeutic interchangeability of generic drugs.
Purpose of the Study:
- To evaluate the in vitro dissolution and in vivo bioavailability relationship for furosemide.
- To assess the bioequivalence of different furosemide (40 mg) oral formulations.
- To determine an appropriate in vitro dissolution medium for furosemide products.
Main Methods:
- A 6x6 crossover bioequivalence study involving 12 healthy volunteers.
- Oral administration of furosemide (40 mg) from six different products (five tablets, one solution).
- Quantification of plasma and urine furosemide concentrations using high-performance liquid chromatography (HPLC) and non-compartmental analysis.
Main Results:
- All tested furosemide tablet formulations showed lower peak plasma concentrations and longer mean residence times compared to the oral solution.
- Bioavailability ranged from 66-96%, with some formulations demonstrating diminished bioavailability.
- All products failed the 75/75 bioequivalence rule, attributed to significant intersubject variability.
- Total urinary furosemide excretion correlated with in vitro drug dissolution at 30 minutes.
Conclusions:
- The in vitro dissolution at pH 5.6 appears to be a suitable dissolution medium for ensuring batch uniformity and bioequivalence of furosemide products.
- The study highlights the importance of in vitro dissolution testing in predicting in vivo performance of furosemide formulations.
- Further investigation into intersubject variability is warranted for furosemide bioequivalence assessments.