Formulation and in Vitro and in Vivo Availability of Diclofenac Sodium Enteric-Coated Beads

Abstract

Diclofenac sodium enteric-coated beads were prepared using the conventional pan coating technique. Eudragit L₁₀₀ was used as a pH-dependent release-controlling polymer. The beads were evaluated for their particle size distribution, drug loading efficiency, flowability, in vitro release in 0.1 N HCI (pH 1.2) and phosphate buffer (pH 6.8), and bioavailability in beagle dogs relative to the commercial enteric-coated tablets Voltaren®. The beads showed a narrow particle size distribution in which 83% of the beads were in the range of 1-2 mm. The actual yield of the beads was 90.5% and their drug loading was 92%. The beads released about 8% of the drug during 2 hr of dissolution in 0.1 N HCI, and the commercial tablets released no drug. In phosphate buffer (pH 6.8) both formulations released their drug content in 1 hr. Both formulations are, therefore, in compliance with the USP requirements for release from enteric-coated dosage forms.

The in vivo availability study in six beagle dogs revealed that the formulated enteric-coated beads filled in hard gelatin capsules had a 197.54% bioavailability relative to that of the commercial Voltaren tablets. The tablets showed a significantly lower (p < 0.05) area under curve for 0—8 hr (AUC_{0-8 hr}) of 13.44 ± 15.02 μg hr/ml compared to 26.55 ± 5.19 μg hr/ml for the capsules. The capsules showed a nonsignificantly (p > 0.05) higher peak plasma concentration (C^max) of 6.77 ± 0.67 μg/ml compared to 5.88 ± 7.38 μg/ml for the tablets. The time to reach peak (T_max) values were 2 ± 1.48 and 2.25 ± 1.08 hr for the capsules and tablets, respectively. The capsules showed less interdog variability with respect to C_max (CV% 34.6) and AUC (CV% 19.55) compared to CV% 79.9 and 111.76, respectively, for the commercial tablets