Research ArticlesComparison of the Absorption of Micronized (Daflon 500® mg) and Nonmicronized 14C‐diosmin Tablets After Oral Administration to Healthy Volunteers by Accelerator Mass Spectrometry and Liquid Scintillation Counting
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INTRODUCTION
Oral absorption is a multifactorial process encompassing not only the in vivo dissolution of the drug, but also the physiological conditions in the gastrointestinal tract such as gastric emptying and the presence of bile acids, as well as the passage of the drug across the intestinal membrane.
The less a drug is absorbed, the more pharmacokinetic variation will occur from one subject to another, and the more it may be influenced by exogenous factors such as diet and dosing regimen.
For highly
Study Drugs and Labeled Compound
Purified flavonoid fraction (S 5682) batch 53879 was supplied by Technologie Servier (Orleans, France). 14C‐labeled diosmin (Fig. 1) was synthesized by Nycomed Amersham Plc. (Buckinghamshire, England). Specific activity was 2.07 GBq/mmol (56 mCi/mmol) with a purity of 98%.
Tablet Preparation
Preparation of the tablet formulations with the radiolabeled drug substance: The tablets were prepared according to a similar process and with the same formulation as that described for the core tablet in the submission file.
Drug Formulation
Manufacture of the tablets was performed to match the specification of the final formulation used in the clinic. The presence of radioactive material, negligible in terms of the individual dose given to the healthy volunteers, still implies formulation on a smaller‐scale machine with adapted safety conditions during the manufacturing process.
The tablets were sampled and tested for purity (radiochemical and nonlabeled drug purity) granulometry, and homogeneity. Radiochemical purity was 98.3% and
CONCLUSIONS
The data reported herein demonstrate that reduction of particle size obtained by a micronization process improves the extent of absorption of diosmin and/or its metabolites, giving a pharmacokinetic explanation to the better clinical efficacy observed with the micronized formulation.
Increasing the absorbed fraction will also lead to lower variability from one patient to another, and less influence of exogenous factors such as diet and dosing regimen.
The results of this study indicate that the
Acknowledgements
CBAMS Ltd. thanks GlaxoSmithKline, Pfizer UK Ltd., Janssen Pharmaceutica Belgium, Novartis Switzerland, the UK Ministry of Agriculture, Fisheries, and Food, and the University of York for their financial assistance in creating our Centre. In addition, we thank Servier, France for giving permission to publish our findings.
REFERENCES (12)
- et al.
A preliminary evaluation of accelerator mass spectrometry in the biomedical field
J Pharm Biomed Anal
(1997) - et al.
Pushing the accelerator: Speeding up drug research with accelerator mass spectrometry
Nucl Inst Methods Phys Res B
(2000) - et al.
A validation study comparing accelerator MS and liquid scintillation counting for analysis of 14C‐labelled drugs in plasma, urine and faecal extracts
J Pharm Biomed Anal
(2000) Micronization: A method of improving the bioavailability of poorly soluble drugs
Methods Find Exp Clin Pharmacol
(1998)Advantage of a micronized flavonoidic fraction (Daflon 500 mg) in comparison with a nonmicronized diosmin
Angiology
(1994)Clinical efficacy of micronized purified flavonoid fraction: An overview
J Vasc Res
(1999)
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