Single-dose pharmacokinetic study of rapidly dispersing diclofenac potassium formulations in healthy volunteers.
OBJECTIVE
The clinical utility of diclofenac potassium, a commonly prescribed analgesic that provides mild to moderate pain relief, may be hindered by its delayed, depressed, and/or inconsistent absorption characteristics. A diclofenac potassium formulation using proprietary dispersion technology (ProSorb) was developed to overcome these limitations. The authors evaluated and compared the pharmacokinetics (PK) of 2 investigational diclofenac potassium liquid filled soft gelatin capsule (DPSGC) preparations and one investigational diclofenac liquid formulation, each incorporating the proprietary dispersion technology, to establish bioequivalence and identify a formulation for further clinical study.


METHODS
In an open-label, single-dose, three-way crossover, relative bioavailability study, 24 healthy volunteers were randomized to receive each of the 25-mg DPSGC formulations (development processes A and B) and the 1-mL (25-mg) liquid diclofenac formulation (similar to the fill liquid used in the DPSGC products) during three inpatient visits. Each dose was separated by 3 days. Plasma samples were collected at preselected time points through 6 hours post dose. Diclofenac concentrations were determined using a validated HPLC method. Bioequivalence was established within the 80% to 125% acceptance range. Safety and tolerability were monitored throughout.


RESULTS
Area under the plasma concentration-time curves (AUC(0-)(t)) for the three formulations were between 577 and 585 ng-hr/mL and peak plasma concentrations (C(max)) were between 958 and 1087 ng/mL, with the DPSGC process B group having the highest C(max). The times to C(max) (t(max)) were all below 30 minutes, with the liquid formulation producing the shortest t(max) (15 minutes). Plasma concentration-time course profiles were similar for all three rapidly dispersing diclofenac potassium formulations. One mild adverse event was observed (lingual paresthesia) and one participant discontinued due to an unrelated event (acute tonsillitis).


CONCLUSIONS
These data show that diclofenac potassium formulations using proprietary dispersion technology are rapidly and consistently absorbed. These characteristics may be beneficial in settings where rapid and consistent drug absorption is desirable. These results may differ in other patient populations such as those experiencing pain or illness.
Lissy
Michael
M
AAIPharma, Inc., Neu-Ulm, Germany.
Stiff
Dwight D
DD
Kowalski
Mark M
MM
Moore
Keith A
KA
D000328:Adult; D000894:Anti-Inflammatory Agents, Non-Steroidal / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D019540:Area Under Curve; D001682:Biological Availability; D018592:Cross-Over Studies; D004008:Diclofenac / Q000008:administration & dosage / Q000009:adverse effects / Q000493:pharmacokinetics*; D005260:Female; D006801:Humans; D057230:Limit of Detection; D008297:Male; D012016:Reference Values
D000894:Anti-Inflammatory Agents, Non-Steroidal; D004008:Diclofenac