ABSTRACT
The aim of this study was to investigate microemulsion (ME) based topical delivery system for fenoprofen calcium (FPCa) to eliminate its oral gastrointestinal adverse effects. ME was prepared by the water titration method using oleic acid as oil phase, tween 80 as a surfactant and propylene glycol as a cosurfactant. Oleic acid was selected as oil phase due to its good solubilizing capacity. ME existence region was determined using pseudo-ternary phase diagrams for preparing different formulations. Six different formulations were selected with various values of oil (25-68%), water (2-3%), and the mixture of surfactant and cosurfactant (1:1) (24-67%). The selected ME formulae were characterized for optical birefringence, transmission electron microscopy (TEM), pH, % transmittance, electronic conductivity, drug content, droplet size, rheological properties and stability evaluation. In vitro release study of FPCa from ME s through the synthetic membrane and hairless rat skin were evaluated. The optimized formula ME5 consisting of 5% w/w FPCa, 60% w/w oleic acid as oil phase, 3% w/w aqueous phase, and 32% w/w of surfactant phase containing Tween 80 and propylene glycol (1: 1) showed the highest transdermal flux and highest skin permeation rate. Finally, the % inhibition of carrageenan-induced rat paw edema of the optimized formula ME5 was highly significant (p < 0.001) as compared to plain gel of FPCa. In conclusion, ME is a promising technique for topical delivery of FPCa.
Subject(s)
Antifungal Agents/pharmacology , Drug Carriers/chemistry , Fenoprofen/pharmacology , Administration, Cutaneous , Animals , Antifungal Agents/administration & dosage , Antifungal Agents/toxicity , Drug Compounding , Drug Liberation , Emulsions , Fenoprofen/administration & dosage , Fenoprofen/toxicity , Hydrogen-Ion Concentration , Liposomes/chemistry , Nanoparticles/chemistry , Oleic Acid/chemistry , Particle Size , Polysorbates/chemistry , Rats , Skin/metabolism , Skin Absorption , Solubility , Surface Properties , Surface-Active Agents/chemistry , ThermodynamicsABSTRACT
El presente trabajo tiene como objetivo describir las características farmacocinéticas, metabólicas y toxicológicas de los ácidos asimétricos aril-2-propiónicos y mostrar la importante variabilidad inter-especies existentes. Además se explican las derivaciones metabólicas del proceso de inversión quiral (camino metabólico de crucial importancia para estos compuestos) y las consecuencias toxicológicas relacionadas con su naturaleza quiral
Subject(s)
Humans , Propionates/chemistry , Anti-Inflammatory Agents, Non-Steroidal/toxicity , Fenoprofen/toxicity , Ketoprofen/toxicity , Molecular Conformation , Serum Albumin , Fenoprofen/metabolism , Fenoprofen/pharmacology , Ketoprofen/metabolism , Ketoprofen/pharmacology , Oxygenases/pharmacology , Prostaglandins/biosynthesisABSTRACT
El presente trabajo tiene como objetivo describir las características farmacocinéticas, metabólicas y toxicológicas de los ácidos asimétricos aril-2-propiónicos y mostrar la importante variabilidad inter-especies existentes. Además se explican las derivaciones metabólicas del proceso de inversión quiral (camino metabólico de crucial importancia para estos compuestos) y las consecuencias toxicológicas relacionadas con su naturaleza quiral (AU)
Subject(s)
Humans , /toxicity , Ketoprofen/toxicity , Fenoprofen/toxicity , Propionates/chemistry , Molecular Conformation , Fenoprofen/pharmacology , Fenoprofen/metabolism , Serum Albumin/drug effects , Ketoprofen/pharmacology , Ketoprofen/metabolism , Oxygenases/pharmacology , Prostaglandins/biosynthesisABSTRACT
Time-course studies on gastric damages in rats caused by nonsteroidal anti-inflammatory drugs (NSAIDs) were performed using a gastroscope, and the readings were quantified to obtain the Congestion-Hemorrhage Index (CHI) for evaluating the potencies of the damaging properties of NSAID. The correlation between CHI and Ulcer Index (UI), the quantified value obtained by the conventional methods, was highly significant at 6 and 24 hr after forced oral administration of NSAID. The peak CHIs of aspirin (300 mg/kg), indomethacin (60 mg/kg), mefenamic acid (300 mg/kg) and fenoprofen calcium (300 mg/kg) appeared approximately 24 hr after a single forced oral administration of drugs. Thus, it was suggested that an observation at 24 hr in addition to one at 6 to 7 hr might be necessary for the examination of damaged gastric mucosa. Under the present experimental conditions, fenoprofen calcium caused the greatest damages on gastric mucosa among the four NSAIDs. Mefenamic acid showed the least damaging potency on gastric mucosa, having a smaller CHI than that of aspirin. Indomethacin possessed a stronger damaging property than aspirin.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Gastric Mucosa/drug effects , Animals , Aspirin/toxicity , Fenoprofen/toxicity , Gastric Mucosa/pathology , Gastrointestinal Hemorrhage/chemically induced , Indomethacin/toxicity , Male , Mefenamic Acid/toxicity , Peptic Ulcer/chemically induced , Rats , Rats, Inbred Strains , Time FactorsABSTRACT
The propionic acids represent the largest chemical class of nonsteroidal anti-inflammatory agents (NSAID). Several of them are widely used, both in the United States and internationally. This paper discusses observations made on fenoprofen, flurbiprofen, ibuprofen and naproxen. Of these compounds, three are racemates; the fourth, naproxen, is an enantiomer. As a group, the propionic acids, along with most members of the other classes of NSAID, produce gastrointestinal damage in most species. These lesions vary from erythema, hemorrhage and erosion to ulceration and peritonitis. As might be expected, the degree of gastrointestinal intolerance depends on many factors: the individual compound, the dose-level, the duration of the period of drug administration, and the pharmacokinetics and metabolism in a given species. For example, in our experience the rat is less tolerant of NSAID than is the monkey, and the dog is less tolerant than the rat. Gastrointestinal lesions have been seen following both parenteral and oral administration; these findings suggest that factors other than local irritation play a role in the development of lesions. Most NSAID inhibit prostaglandin cyclo-oxygenase activity, which results in a prostaglandin deficiency at the tissue level. The administration of relevant exogenous prostaglandins, such as 16,16-dimethyl PGE2, has been shown to inhibit the gastrointestinal toxicity accompanying the administration of several NSAID, including some of the propionic acids.
Subject(s)
Anti-Inflammatory Agents, Non-Steroidal/toxicity , Digestive System/drug effects , Propionates/toxicity , Animals , Digestive System/pathology , Dogs , Fenoprofen/toxicity , Flurbiprofen/toxicity , Haplorhini , Ibuprofen/toxicity , Naproxen/toxicity , Rats , Species SpecificityABSTRACT
The efficacy and safety of fenoprofen calcium (Nalfon, Dista, Indianapolis, IN) and aspirin for treating acute inflammatory soft tissue injuries were compared in a 3 to 10-day randomized, double-blind, parallel study of 100 patients with bruise (1), bursitis (33), ligamentous strain (8), myofascitis (43), and tendinitis (15). Forty-seven of the 50 aspirin-treated and 48 of the 50 fenoprofen-treated patients were evaluable. Results of the study showed that fenoprofen calcium and aspirin were equally effective in treating acute inflammatory soft-tissue injuries; however, adverse experiences occurred in fewer patients and at a lower frequency with fenoprofen calcium therapy. In global assessments, 73% of the patients rated fenoprofen therapy as very good or good compared to 64% of the patients who received aspirin therapy. There were no significant differences in the clinician's and the patients' global assessments of therapy. The study suggests that fenoprofen calcium is effective for use in treating soft-tissue injuries since it is better tolerated than aspirin when given in equally effective doses.
Subject(s)
Aspirin/therapeutic use , Fenoprofen/therapeutic use , Phenylpropionates/therapeutic use , Wounds and Injuries/drug therapy , Adult , Aged , Aspirin/toxicity , Clinical Trials as Topic , Double-Blind Method , Female , Fenoprofen/toxicity , Humans , Inflammation , Male , Middle Aged , Pain/physiopathology , Wounds and Injuries/physiopathologySubject(s)
Anti-Inflammatory Agents/toxicity , Oxazines/toxicity , Stomach Ulcer/chemically induced , Animals , Benzoxazines , Biotransformation , Fenoprofen/toxicity , Ibuprofen/toxicity , Indomethacin/toxicity , Male , Naproxen/toxicity , Oxazines/analogs & derivatives , Oxazines/metabolism , Peptic Ulcer Hemorrhage/chemically induced , Phenylbutazone/toxicity , Rats , Salicylates/toxicity , Time Factors , Tolmetin/toxicityABSTRACT
Sixteen men received 3904 mg of aspirin, 2400 mg of fenoprofen, or placebo daily for 1 week in a double blind and crossover trial. Fecal blood loss was measured by 51Cr labeled red cells; gastric and duodenal pathology were observed endoscopically. There was more (P less than 0.05) blood loss (4.96 ml) after aspirin than after fenoprofen (2.46 ml) or placebo (0.79 ml). By endoscopic examination, aspirin induced more (P less than 0.05) gastrointestinal pathology than fenoprofen or placebo, and there was a correlation of 0.70 between the two methods used in this study.
