salicylates and glycol-salicylate

A combination of the active agents arnica and hydroxyethyl salicylate (HES) in ethanolic solution (Sportino Acute Spray) is cutaneously applied for the treatment of sports injuries and diseases of the locomotor apparatus. The aim was to examine the efficacy and synergism of the single substances and the combination with regard to the analgesic effect after cutaneous application as well as to validate the method of transcutaneous electronic stimulation as a method of measuring the analgesic effect. In the present article, the method of transcutaneous electrostimulation was used in a randomized, controlled, single-blind trial on healthy volunteers to provide objective evidence that the combination of active agents displays a significantly greater analgesic effect than the individual active agents. Thus there is synergy between the active agents arnica and hydroxyethyl salicylate in the combination preparation. In addition, the effect of the vehicle ethanol and the reference substance water could be determined within the framework of these comparative experiments and the difference between the combination preparation and the individual substances arnica and HES could be shown. The method of transcutaneous electrostimulation used for the objective measurement of the analgesic effect was validated.

Topics: Administration, Topical; Adolescent; Adult; Aged; Analgesics, Non-Narcotic; Arnica; Cross-Over Studies; Drug Synergism; Electric Stimulation; Ethanol; Female; Humans; Male; Middle Aged; Pain Threshold; Plant Extracts; Reproducibility of Results; Salicylates; Single-Blind Method; Solvents

Two clinical studies were carried out to investigate the efficacy and safety as well as the local and systemic availability of a hydroxyethylsalicyclate gel. A double blind, multicenter trial, involving 113 patients with nonarticular rheumatic back pain, revealed statistically significant relief of pain as compared with placebo. Local and systemic tolerance was excellent. An open study of bioavailability after local application in 16 patients showed a mean salicylate concentration of 0.93 +/- 0.5 microgram/ml in the synovial fluid and 0.40 +/- 0.23 microgram/ml in the synovial membrane, compared with 0.14 +/- 0.04 microgram/ml in the serum. Genetisinic acid was not detected, while OH-hippuric acid was detected only in the serum and synovial fluid.

Topics: Administration, Topical; Adult; Aged; Anti-Inflammatory Agents, Non-Steroidal; Arthritis, Rheumatoid; Biological Availability; Double-Blind Method; Female; Gels; Humans; Male; Middle Aged; Pain Measurement; Salicylates

In this work, we developed a number of generalised skin diffusion based pharmacokinetic models to relate published in vivo urinary excretion data to matching experimentally generated in vitro human skin permeation test (IVPT) data for a series of topically applied salicylate esters. A simplified linear in vivo model was found to inadequately describe the time course of urinary excretion over the entire sampling period. We represented the skin barrier as both a one layer (stratum corneum) and a two-layer (stratum corneum with viable epidermis) diffusion model and convoluted their Laplace solutions with that for a single exponential disposition phase to describe the urinary excretion profiles in the Laplace domain. We also derived asymptotic approximations for the model and estimated the conditions under which they could be used. We then sought to develop in vitro - in vivo relationships (IVIVR) for topically applied methyl, ethyl and glycol salicylates using our experimental IVPT data and the literature urinary excretion data. Good linear IVIVRs for ethyl and glycol salicylates were obtained, but the IVIVR for methyl salicylate was poor, perhaps because of topical stimulation of local skin blood flow by methyl salicylate. The ratio of the hydrated to dehydrated skin permeation for all salicylate esters was the same in both the IVPT and in vivo studies. A diffusion based one compartment pharmacokinetic model was also developed to describe the urinary excretion of solutes after removal of topical products and to compare the methyl salicylate skin permeation for five different body sites. The work presented here is consistent with the development of skin IVIVRs, but suggests that different skin conditions, application sites and local skin effects may affect model predictions.

Topics: Administration, Cutaneous; Diffusion; Female; Humans; Models, Biological; Permeability; Salicylates; Skin; Skin Absorption

Capsaicinoids, salicylic acid, methyl and ethyl salicylate, glycol monosalicylate, camphor and l-menthol are widely used in topical formulations to relieve local pain. For each separate compound or simple mixtures, quantitative analysis methods are reported. However, for a mixture containing all above mentioned active compounds, no assay methods were found. Due to the differing physicochemical characteristics, two methods were developed and optimized simultaneously. The non-volatile capsaicinoids, salicylic acid and glycol monosalicylate were analyzed with liquid chromatography following liquid-liquid extraction, whereas the volatile compounds were analyzed with static headspace-gas chromatography. For the latter method, liquid paraffin was selected as compatible dilution solvent. The optimized methods were validated in terms of specificity, linearity, accuracy and precision in a range of 80% to 120% of the expected concentrations. For both methods, peaks were well separated without interference of other compounds. Linear relationships were demonstrated with R² values higher than 0.996 for all compounds. Accuracy was assessed by performing replicate recovery experiments with spiked blank samples. Mean recovery values were all between 98% and 102%. Precision was checked at three levels: system repeatability, method precision and intermediate precision. Both methods were found to be acceptably precise at all three levels. Finally, the method was successfully applied to the analysis of some real samples (cutaneous sticks).

Topics: Analgesics, Non-Narcotic; Camphor; Capsaicin; Chromatography, Gas; Chromatography, Liquid; Liquid-Liquid Extraction; Menthol; Ointments; Pharmaceutical Preparations; Salicylates; Salicylic Acid; Sensitivity and Specificity

Topics: Anti-Inflammatory Agents; Dermatitis, Allergic Contact; Gels; Humans; Male; Middle Aged; Patch Tests; Salicylates; Veterinary Drugs

Topics: Administration, Topical; Allergens; Anti-Inflammatory Agents; Anti-Inflammatory Agents, Non-Steroidal; Dermatitis, Allergic Contact; Drug Combinations; Female; Follow-Up Studies; Gels; Humans; Middle Aged; Patch Tests; Risk Assessment; Salicylates; Sensitivity and Specificity

The penetration of active ingredients from topically applied anti-inflammatory pharmaceutical products into tissues below the skin is the basis of their therapeutic efficacy. There is still controversy as to whether these agents are capable of direct penetration by diffusion through the tissues or whether redistribution in the systemic circulation is responsible for their tissue deposition below the application site.. The extent of direct penetration of salicylate from commercial ester and salt formulations into the dermal and subcutaneous tissue of human volunteers was determined using the technique of cutaneous microdialysis. We also examined differences in the extent of hydrolysis of the methylester of salicylate applied topically in human volunteers and in vitro skin diffusion cells using full-thickness skin and epidermal membranes.. The present study showed that whilst significant levels of salicylate could be detected in the dermis and subcutaneous tissue of volunteers treated with the methylsalicylate formulation, negligible levels of salicylate were seen following application of the triethanolamine salicylate formulation. The tissue levels ofsalicylate from the methylsalicylate formulation were approx. 30-fold higher than the plasma concentrations.. The absorption and tissue concentration profiles for the commercial methylsalicylate formulation are indicative of direct tissue penetration and not solely redistribution by the systemic blood supply.

Topics: Administration, Topical; Adult; Cells, Cultured; Diffusion; Female; Humans; Hydrolysis; In Vitro Techniques; Male; Microdialysis; Salicylates; Skin; Skin Absorption

Topics: Administration, Topical; Anti-Inflammatory Agents; Dermatitis, Allergic Contact; Humans; Male; Middle Aged; Patch Tests; Salicylates

Three radioactively marked substances (on the basis of a carbopol gel, 80% water - isopropanol) were analyzed comparatively in regard to the penetration of ethyleneglycolmonosalicylate and benzylnicotinate to intact and impaired human skin. The objective of the in-vitro study was to gain evidence on possible interaction of the locally applied substances upon skin penetration. Only 5 h after application ethyleneglycolmonosalicylate reaches a steady state of concentration in the corium of approximately 700-800 mumol/l tissue which is maintained (in contrast to nicotinate) even after 16 h exposure time. Benzylnicotinate reaches its maximum concentration (100-200 mumol/l tissue in all living layers of the skin) 100-300 min after application. After simultaneous local application of both substances the penetration of ethyleneglycolmonosalicylate in corium and subcutis is clearly intensified by benzylnicotinate. Substance distribution in skin cross section and kinetics do not change. Penetration of benzylnicotinate however, is delayed by the salicylate (especially at exposure time of 100-300 min). Results of comparative penetration studies with inverted skin (inverse penetration), intact and impaired (stripped) skin allow the following conclusion: penetration limiting of salicylate occurs in the horny layer only due to the optimal liberation. Penetration of nicotinate on the other hand, is already prevented "before" the skin because of insufficient liberation from the vehicle.

Topics: Drug Interactions; Ethylene Glycols; Humans; Nicotinic Acids; Salicylates; Skin; Time Factors