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.
Novartis Institutes for Biomedical Research, Hyderabad, India.
Girish
G
Bende
Novartis Institutes for Biomedical Research, Hyderabad, India.
Shibadas
S
Biswal
Novartis Institutes for Biomedical Research, Cambridge, MA, USA.
Prafulla
P
Bhad
Novartis Pharma Co., Beijing, China.
Yuming
Y
Chen
Novartis Institutes for Biomedical Research, Hyderabad, India.
Atish
A
Salunke
Novartis Institutes for Biomedical Research, Basel, Switzerland.
Serge
S
Winter
Novartis Pharmaceuticals, East Hanover, NJ, USA.
Robert
R
Wagner
Novartis Institutes for Biomedical Research, East Hanover, NJ, USA.
Gangadhar
G
Sunkara
D000284:Administration, Oral; D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage* / Q000493:pharmacokinetics; D019540:Area Under Curve; D001682:Biological Availability; D002214:Capsules; D002853:Chromatography, Liquid / Q000379:methods*; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage* / Q000493:pharmacokinetics; D006801:Humans; D008297:Male; D013607:Tablets; D053719:Tandem Mass Spectrometry / Q000379:methods*; D055815:Young Adult
D000894:Anti-Inflammatory Agents, Non-Steroidal; D002214:Capsules; D013607:Tablets; D004008:Diclofenac
diclofenac potassium; pharmacokinetics; soft gelatin capsule