Pharmacokinetics of Diclofenac after Oral Administration of its Potassium Salt in Sachet and Tablet Formulations

Abstract

This paper reports the results of a pharmacokinetic study involving 24 healthy volunteers and designed to characterise the rate and extent of diclofenac absorption after the administration of a single dose of diclofenac (CAS 15307-86-5) potassium salt 50 mg in sachet (Voltfast) and tablet (Cataflam) formulations. Timed plasma concentrations of diclofenac during a 12-h-period after dosing were measured by means of HPLC with UV detection at 275 nm and a quantification limit of 10 ng/ml; the method was fully validated for pharmacokinetic purposes. These plasma concentrations were used to calculate Cmax, tmax, trapezoidal AUC0-t and AUC0-infinity and t1/2 by means of noncompartmental analysis. Cmax and tmax are the parameters expressing the rate of absorption, whereas the AUCs reflect the extent of absorption. The rate of absorption with the sachets proved to be very fast, reaching peak values at 10 min in seven subjects and at 15 min in the remaining subjects: mean time was 13.68 min, with concentrations at 5 min being 38% of Cmax. The average time to peak concentration with the tablets was 53.10 min. The extent of absorption of the sachets and tablets was similar, with AUC0-infinity values of respectively 1362 and 1214 ng.ml-1.h, and a 90% confidence interval 1.05-1.20. The highly soluble potassium salt of diclofenac was rapidly absorbed, especially in its sachet formulation, and thus appears to be an invaluable analgesic agent that is particularly useful for quick pain relief.

Advance Delivery System Dosage Form for Analgesic, Their Rationale, and Specialty

“…More than one dosage forms may exist for a single particular drug. This is due to the fact that different clinical conditions may need different routes of administration [8]. For example, where there is a condition of nausea or vomiting, it may be difficult to use an oral dosage form.…”

“…These conventional drug delivery systems provide immediate release of the drug without controlling the rate or drug release. A number of doses given daily in order to achieve and maintain therapeutic level to achieve effective plasma concentrations cause fluctuations in plasma levels of the drug [8][9][10] and drug plasma levels could fall below the minimum effective concentration and can also exceed the minimum toxic concentration (Figure 1). …”

“…The need for fewer administrations of analgesic or optimal use of analgesic toward "no pain" maintenance is to avoid adverse side effect and indirectly to increase patient compliance in their pain management [8].…”

“…A good example would be the sustenance of release preparation of diclofenac sodium for oral administration [8].…”

Diclofenac potassium for oral solution (CAMBIA®) in the acute management of a migraine attack: clinical evidence and practical experience

“…27 When compared with the diclofenac potassium tablet, the oral solution reached maximum plasma concentrations approximately 80% faster; exposure was similar between the 2 formulations. 26,28 Clinical studies of diclofenac for the acute treatment of a migraine attack The efficacy and safety of diclofenac potassium in the acute treatment of a migraine attack has been evaluated in 4 placebo-or active-controlled studies, including 2 studies that used different formulations 29,30 and 2 registration studies of diclofenac potassium for oral solution. 31,32 Diclofenac potassium sugar-coated tablets were evaluated in 144 patients with migraine with or without aura.…”