Alclofenac Research Articles

In‐vitro Zero‐order Release of Anti‐inflammatory Drugs From Pullulan Acetate Phthalate Microspheres

Pullulan acetate phthalate (PAP) was synthesized, and applied as a wall material for microencapsulation of anti-inflammatory drugs, alclofenac, ketoprofen and ibuprofen using an oil-in-oil (%) emulsion solvent evaporation process. In relation to all drugs, the dissolution pattern from microspheres prepared with PAP which contains a phthalyl content between 13 and 16% and an acetyl content between 30 and 33%, showed an apparent zero-order release until almost 80% drug was released into the pH 6.8 medium described in the disintegration test in JP XIII. The dissolution mechanism of such an apparent zero-order dissolution profile could be explained by the Case-II transport mechanism in the category of swelling controlled system in the classification related to controlled polymeric systems.

Enhancement effect of an ethanol/Panasate 800 binary vehicle on anti-inflammatory drug permeation across excised hairless mouse skin.

The novel binary vehicle system consisting of ethanol (EtOH) and Panasate 800 as tricaprylin was applied to five types of nonsteroidal anti-inflammatory drugs, and its enhancing effect on drug permeation across hairless mouse skin in vitro was assessed. The permeability of all drugs was remarkably increased by the treatment of skin with EtOH/Panasate 800 binary systems compared with either EtOH or Panasate 800 alone, and the effect reached a maximum in EtOH/Panasate 800 (40/60) system. With regard to this binary system, the skin permeation ratio or flux of the drug increased in the following order: salicyluric acid (SU) > salicylic acid (SA) > alclofenac (ALC) > ketoprofen (KP) > ibuprofen (IBU). The one-layer skin model was applied concerning the above skin permeation profiles of the five drugs. Diffusion parameter (D'), partition parameter (K'), and permeation constant (Kp = D' x K') were calculated using the Laplace-transformed equations with the aid of MULTI (FILT). It was well demonstrated that the reduction of lag time and the increase of flux caused by EtOH/Panasate 800 binary vehicle systems was due to an increase of D' value by Panasate 800 and K' value by EtOH, respectively, in the skin. Especially, the EtOH/Panasate 800 (40/60) binary vehicle system produced the largest Kp value in each drug. In relation to all the EtOH/Panasate 800 binary vehicle systems, the logarithms of calculated Kp were found to be in inverse proportion to the logarithms of a n-octanol/water partition coefficient (P) of the drug which appeared in previous literature.

Heterotropic binding of alclofenac and dansylsarcosine to bovine serum albumin

The binding data for the interaction of alclofenac (AF) and dansylsarcosine (DS) to bovine serum albumin (BSA) have respectively yielded nonlinear Scatchard plots. The plots have been subjected to Rosenthal’s method of analysis and thus the ligands have been found to possess two different kinds of sites in BSA. The binding capacities of these sites have been evaluated. The fluorescence competition studies have revealed that the binding of DS to BSA is noncompetitively inhibited by AF. Therefore, the presence of distinct binding sites for AF and DS in BSA could be inferred. The fluorescence quenching studies have also been able to demonstrate this aforesaid fact. The analysis of the quenching data by the modified Stern-Volmer plot has indicated that both the tryptophan (Trp) residues of BSA are accessible to DS for the quenching in absence of AF, but only one of them is accessible in presence of AF. This has led to suggest that the binding site of DS has been in the vicinity of loop 3–4, involving Trp-134 and Trp-212. The binding of AF at a distinct site from that of DS has exerted heterotropic interactions at the DS binding site and thereby inhibited the binding of DS to BSA.

Platelet antiaggregating activity of Alclofenac: A preliminary pharmacodynamic and kinetic study in rabbit

Summary A non steroidal antiinflammatory agent, Alclofenac (ALCLO), is examined for its inhibitory activity on collagen induced platelet aggregation. Employing “in vitro” techniques, the extent of the ALCLO inhibition is indipendent of incubation time (IC50 = 8.8 · 10−4 M). In contrast, the effect of two other antiinflammatory drugs, acetylsalicylic acid (ASA) and ibuprofen (IBU), is enhanced with extended incubation time. Therefore, ALCLO is equally effective with short incubation (2 min) and at least 80 times less potent than ASA and IBU after long incubation (60 min). ALCLO activity is then studied in “ex vivo” experiments after dosing in rabbit. Drug plasma levels and effects on platelet aggregation are simultaneously determined. After single i.v. injection, plasma elimination kinetics of ALCLO is well correlated with the loss of the antiaggregating activity. Infusion of the drug at three different steady state levels, shows a similar behaviour.