Robert Frank Wagner

Relative bioavailability of diclofenac potassium from softgel capsule versus powder for oral solution and immediate‐release tablet formulation

The oral bioavailability of diclofenac potassium 50 mg administered as a soft gelatin capsule (softgel capsule), powder for oral solution (oral solution), and tablet was evaluated in a randomized, open‐label, 3‐period, 6‐sequence crossover study in healthy adults. Plasma diclofenac concentrations were measured using a validated liquid chromatography–mass spectrometry/mass spectrometry method, and pharmacokinetic analysis was performed by noncompartmental methods. The median time to achieve peak plasma concentrations of diclofenac was 0.5, 0.25, and 0.75 hours with the softgel capsule, oral solution, and tablet formulations, respectively. The geometric mean ratio and associated 90%CI for AUCinf, and Cmax of the softgel capsule formulation relative to the oral solution formulation were 0.97 (0.95–1.00) and 0.85 (0.76–0.95), respectively. The geometric mean ratio and associated 90%CI for AUCinf and Cmax of the softgel capsule formulation relative to the tablet formulation were 1.04 (1.00–1.08) and 1.67 (1.43–1.96), respectively. In conclusion, the exposure (AUC) of diclofenac with the new diclofenac potassium softgel capsule formulation was comparable to that of the existing oral solution and tablet formulations. The peak plasma concentration of diclofenac from the new softgel capsule was 67% higher than the existing tablet formulation, whereas it was 15% lower in comparison with the oral solution formulation.

Bioavailability of valsartan oral dosage forms.

The oral bioavailability of valsartan from extemporaneous suspension and solution formulations were evaluated relative to tablet formulation in two separate open‐label, randomized crossover studies in healthy adults. In both studies, the plasma concentrations of valsartan after oral administration were analyzed using validated liquid chromatography‐tandem mass spectrometry (LC–MS/MS) methods, and the corresponding pharmacokinetic parameters were estimated using noncompartmental analysis. The peak plasma concentration (Cmax) and area under the concentration time‐curves (AUC(0–∞)) of valsartan from the extemporaneous suspension were higher by 1.93‐ and 1.56‐fold, respectively, relative to the tablet formulation (P < .001). The Cmax and AUC(0–∞) of valsartan from the oral solution were higher by 2.21‐ and 1.74‐fold, respectively, relative to the tablet formulation (P < .001). These results indicate that both rate and extent of absorption of valsartan are higher in the two liquid dosage forms (extemporaneous suspension and solution formulations) relative to the solid oral dosage form (tablet formulation).