Comparative bioavailability study of three brand products of diclofenac sodium 50mg oral tablets in healthy volunteers

الملخص EN

Background : poor quality medicines could be substandard, degraded or counterfeit medicines.

One of the measures used to detect poor quality drugs is comparison with a reference product taking pharmacokinetic end points in consideration.

Objectives : to compare the bioavailability of three brand products of diclofenac sodium 50mg oral tablets in healthy volunteers.

One of these brands is locally manufactured.

The other two are from known foreign drug manufacturers.

Methods : A randomized, three-way, cross-over bioavailability study was performed on 10 apparently healthy male volunteers.

Each received successively, a single oral tablet of 50 mg diclofenac sodium from the three sources with a washout interval of one week.

Blood samples were taken until six hours after drug administration and analyzed using HPLC system (Agilant, model 1200-USA, with an Agilent 1200 variable wavelength detector and a Zorbax Eclipse XBD-C18 column).

Quantitation was achieved by measurement of the peak height ratios of the drug to ibuprofen as internal standard.

The amount of diclofenac sodium in each of the three drug products was also measured in vitro.

Results : maximum plasma concentration (Cmax) was significantly different among the three tablets with the main difference was between the locally manufactured tablet and the two other tablets (0.72 μg / ml for the locally manufactured product compared with 1.55 and 1.24 μg / ml for the reference products).

Time to reach maximum concentration (Tmax) showed no significant difference between the three brands of diclofenac sodium tablets.

The area under the curve differs significantly between the three products.

The area under plasma concentration-time curve (AUC) of the locally manufactured product represented 64.7 % and 74 % of the AUC of the two reference brands.

The plasma elimination half-life (t ½) differs among the three different types of products but these differences ran short of statistical significance (P < 0.058).

In vitro assay of the amount of diclofenac sodium in each tablet showed no significant differences between the three types of tablets.

Conclusion : the locally manufactured enteric coated diclofenac tablet is not interchangeable with the two reference foreign brand products, although they contain approximately the same amount of diclofenac sodium.

It is speculated that differences in bioavailability and in peak drug levels might be attributed to pharmaceutical factors such as the rate of disintegration and dissolution which can be affected by the types of additives and the coating materials in each tablet.