Single-dose pharmacokinetic study of rapidly dispersing diclofenac potassium formulations in healthy volunteers

Abstract

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.

* Xanodyne Pharmaceuticals, Inc., Newport, Kentucky, USA, licensed from AAIPharma, Inc, Natick, Massachusetts, USA.

Research design and 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.

Key words: :

• Bioequivalence
• Diclofenac potassium
• Dispersion technology
• Pharmacokinetics
• ProSorb

Transparency

Declaration of funding

This study was funded by AAIPharma, Inc., Wilmington, NC, USA.

Declaration of financial/other relationships

M.L. and D.D.S. have disclosed that they are full-time employees of AAIPharma, Inc. M.M.K. has disclosed that at the time of the study he was a full-time employee of AAIPharma and now is a full-time employee of Viventia Biotechnologies, Inc. He has equity ownership of AAIPharma. K.M. has disclosed that he is a full-time employee of Xanodyne Pharmaceuticals, Inc.

All peer reviewers receive honoraria from CMRO for their review work. The peer reviewers have disclosed that they have no relevant financial relationships.

Acknowledgment

Editorial assistance was provided by Scott Billecke, PhD, The JB Ashtin Group, Inc., Plymouth, MI, USA, which was funded by Xanodyne. The authors thank the participants, coordinators, nurses, and investigators involved in this study.

Notes

* Xanodyne Pharmaceuticals, Inc., Newport, Kentucky, USA, licensed from AAIPharma, Inc, Natick, Massachusetts, USA.

* Xanodyne Pharmaceuticals, Inc., Newport, Kentucky, USA, licensed from AAIPharma, Inc, Natick, Massachusetts, USA.