Pharmacokinetic comparison of an oral diclofenac potassium liquid-filled soft gelatin capsule with a diclofenac potassium tablet.

OBJECTIVE: To compare the pharmacokinetic profiles of diclofenac potassium liquid-filled soft gelatin capsules (DPSGC) using patented ProSorb dispersion technology with an immediate-release, diclofenac potassium 50-mg comparator tablet in two open-label, single-dose, randomized, crossover relative bioavailability studies in healthy volunteers. METHODS: In Study 1, volunteers (n = 21) received DPSGC 50 mg or a diclofenac potassium 50-mg comparator tablet in two inpatient study periods. In Study 2 (n = 54), volunteers received DPSGC 25 mg, DPSGC 50 mg, or a diclofenac potassium 50-mg comparator immediate-release tablet in three inpatient study periods. RESULTS: In both studies, DPSGC 50 mg displayed a significantly shorter T(max) and higher C(max) than the 50-mg diclofenac potassium comparator tablet. DPSGC 25 mg (Study 2) produced a shorter T(max) (0.45 h) and an equivalent C(max) (1125 ng/ml) to the 50-mg comparator drug. Plasma diclofenac concentration-time courses for the diclofenac potassium 50-mg comparator tablet showed many low, delayed, or multiple peaks compared with DPSGC treatments. CONCLUSIONS: DPSGC 25 mg and 50 mg were more rapidly and consistently absorbed than diclofenac potassium 50-mg comparator tablets. The C(max) of DPSGC 25 mg was equivalent to the 50-mg diclofenac potassium comparator tablet. These characteristics may be beneficial when fast, consistent drug absorption is needed.

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. 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.

Determination of guaifenesin in human serum by capillary gas chromatography and electron capture detection.

A method for the quantitation of guaifenesin in human serum has been developed and validated. The procedure involves liquid-liquid extraction of the serum sample in the presence of mephenesin as an internal standard, followed by derivatization and analysis using capillary gas chromatography (GC) and electron capture detection (ECD). Different solvents were tested for extraction of guaifenesin from serum. n-Hexane/dichloromethane (1:1, v/v) gave the highest recovery and the lowest background and was chosen as the extraction solvent. After extraction, the residue of guaifenesin was derivatized at 60 degrees C for 30 min, with trifluoroacetic acid anhydride (TFAA) in toluene in the presence of pyridine. Excess trifluoroacetic acid anhydride was removed using dilute solution of ammonium hydroxide. The method proved to be linear over the range of 25.0-1000 ng/ml. Recovery of guaifenesin from spiked samples was consistent, averaging 75.5% at 50.0 ng/ml with a range of 72.0-80.0% (N = 8 determinations) and averaging 78% at 800 ng/ml with a range of 76.0-81.0% (N = 8 determinations). The internal standard recovery was also consistent averaging 72.8% with a range of 67.0-76.0% (N = 16 determinations).