Percutaneous Absorption Of Piroxicam Research Articles

Penetration-Enhancing Effect of the Essential Oil and Methanolic Extract of Eryngium bungei on Percutaneous Absorption of Piroxicam through Rat Skin

Recently, in order to improve drug permeation through the skin, penetration enhancers have attracted a great deal of interest in increasing percutaneous absorption. Natural compounds like terpenes have been suggested as promising non-toxic, non-irritating transdermal penetration enhancers. This investigation aimed to study the effect of extract and essential oil of Eryngium bungei (as a traditional anti-inflammatory and antinociceptive) on the transdermal absorption of piroxicam. The stable gel was chosen and enhancing effects of plant extract and essential oil with different concentrations (0.5 - 3.0 and 0.25 - 5.0 % w/w respectively) on the permeation of piroxicam were evaluated. The results showed that the greatest enhancement of the skin transport occurs at the highest concentration of the enhancer (P < 0.01). The most outstanding penetration enhancer was plant essential oil in 5 % w/w, providing an almost 9.17-fold increase in permeability coefficient of piroxicam.

Effect of the Essential Oil of Eryngium caeruleum on Percutaneous Absorption of Piroxicam through Rat Skin

Recently, in order to improve drug permeation trough the skin, penetration enhancers have attracted a great deal of interest in increasing percutaneous absorption. Natural compounds like terpenes have been suggested as promising non-toxic, non-irritating transdermal penetration enhancers. This investigation aimed to study the effect of different concentrations of essential oil of Eryngium caeruleum on the transdermal absorption of piroxicam. Piroxicam solubility was evaluated and several formulations were developed. The stable gel was chosen and enhancing effects of essential oil with different concentrations (0.25–5.0 % w/w) on the permeation of piroxicam were evaluated using Franz diffusion cells fitted by rat skin. PEG 200: buffer 7.4 (40:60) were used as suitable solvent for selected formulation. The results showed that in all cases (formulations containing plant essential oil) the greatest enhancement of the skin transport occurs at the highest concentration of the enhancer (P < 0.01). There is no direct linear relationship between E. caeruleum essential oil and the permeation rate. The most outstanding penetration enhancer was plant essential oil in 5 % w/w, providing an almost 8.56-fold increase in permeability coefficient of piroxicam. E. caeruleum essential oil have shown ability to enhance the permeation of piroxicam across rat skin. Based on anti-inflammatory and analgesic effects of this genus, and traditional uses, the enhancer effects of E. caeruleum will be emphasized.

Influence of vehicles on the in vitro percutaneous absorption of piroxicam to optimise the formulation of patch tests in dermatology

AbstractThe present study evaluated the influence of various vehicles on the in vitro percutaneous absorption of piroxicam across human skin under standard diffusion conditions to optimise the formulation of patch tests in dermatology. The transdermal permeation properties of piroxicam were evaluated from five vehicles (PEG 400, propylene glycol, transcutol P, petrolatum, and petrolatum + transcutol P 10%) using Franz diffusion cells. Piroxicam was applied as a saturated solution in vehicles to ensure equal thermodynamic activity of piroxicam in the vehicles. Concentrations of piroxicam were determined by high performance liquid chromatography in epidermis, dermis, and receptor liquid. The release of piroxicam from its vehicles and consequently its cutaneous absorption are influenced by the vehicle assayed and the solubility of piroxicam in each vehicle. The penetration of piroxicam through human skin was clearly enhanced by propylene glycol and petrolatum + transcutol P 10%, with cumulated amounts of piroxicam in the receptor fluid at 48 h of 116±32 and 159±28 μg/mg/cm2 respectively, whereas petrolatum alone did not allow the diffusion of piroxicam. Additional experiments should be conducted in vivo to correlate the results obtained in vitro and to provide clinicians with a more reliable diagnostic test. Drug Dev. Res. 58:283–290, 2003. © 2003 Wiley‐Liss, Inc.

An Investigation into the Effect of Various Penetration Enhancers on Percutaneous Absorption of Piroxicam

Achieving a desirable percutaneous absorption of drug molecule is a major concern in formulating dermatological products. The use of penetration enhancers could provide a successful mean for this purpose. The aim of this study was to evaluate the effect of incorporating a few common penetration enhancers (in different concentrations) into a 0.5% w/w piroxicam (model drug) gel formulation, on the permeability rate of drug through rat abdominal skin in vitro. For this purpose various concentrations of oleic acid (OA), urea (UR), lecithin (LEC) and isopropyl myristate (IPM) were used as the penetration enhancer. In order to investigate the effect of penetration enhancers used in this study on the permeability rate of piroxicam through sections of excised rat skin, Franz-type diffusion cells were employed. The receptor phase was constantly stirring 0.9% w/v sodium chloride solution at 32°C. At set intervals up to 8h, 5ml samples were removed from the receptor compartment and the amount of piroxicam permeated through the skin calculated by determining the UV absorbance of drug at 353 nm. Results show that among the penetration enhancers used, the use of OA at a concentration of 1.0% w/w had the greatest effect on the permeability rate of piroxicam, and produced the highest enhancement ratio among all the penetration enhancers examined. The other penetration enhancers used were found to have a far smaller effect on the permeability rate of piroxicam through rat skin. The enhancement ratio of the penetration enhancers used in the formulation of piroxicam gel were found to increase in the order of OA>> IPM > LEC > UR.

Effect of ethanolamine salts and enhancers on the percutaneous absorption of piroxicam from a pressure sensitive adhesive matrix

The effects of salt formation on the percutaneous absorption of piroxicam through hairless mouse skin from a pressure sensitive adhesive (PSA) matrix were investigated. We also studied the effect of permeation enhancers on the skin permeation of piroxicam or piroxicam-ethanolamine (PX-EA) salts from an acrylic adhesive matrix. The order of the permeation rates of piroxicam and PX-EA salts from the PSA matrix was piroxicam-monoethanolamine salt (PX-MEA)>piroxicam-diethanolamine salt (PX-DEA)>piroxicam>piroxicam-triethanolamine salt (PX-TEA). The enhancer Crovol ® A40 provided the highest piroxicam and PX-MEA fluxes and Plurol oleque ® the highest PX-DEA and PX-TEA fluxes. The order of piroxicam and PX-EA salts permeabilities were different for saturated solutions in various enhancers and PSA matrix containing the same enhancer, especially when Crovol A40, Crovol ® PK40 or Plurol oleque were used as enhancers. No close relationship was found between the fluxes of piroxicam or PX-EA salts from saturated solutions and from PSA matrices containing the same enhancer. Maximum piroxicam flux was obtained when PX-MEA/PX-TEA (4:6, v/v) was incorporated into a PSA matrix containing Crovol ® PK40.

Effect of skin pretreatment with fatty acids on percutaneous absorption and skin retention of piroxicam after its topical application

The enhancing effect of several fatty acids from different subclasses: saturated (lauric acid), mono-unsaturated (oleic acid) and poly-unsaturated (linoleic and linolenic acids) in the percutaneous absorption of piroxicam was investigated. These fatty acids were applied on the skin membrane in three different ways: included in the vehicle, as a pretreatment or both. An increase in piroxicam flux value was found for lauric and oleic acids in the following order: skin pretreatment with 5% fatty acids followed by application of gels containing 5% fatty acids>skin pretreatment with 5% fatty acids followed application of control gel>gel containing 5% fatty acids without skin pretreatment. For linoleic and linolenic acids, the piroxicam flux in the two pretreatment experiments was almost the same, although higher than when fatty acids were included in the formulation. Skin pretreatment with 5% linolenic acid in propylene glycol followed by application of control gel or a gel containing 5% linolenic acid, showed the highest enhancing capacity. After skin pretreatment with fatty acids, the lag time values decreased nearly three times compared to those obtained when the same fatty acids were included in the formulation. The amount of piroxicam retained in the skin after pretreatment with fatty acids was found to be very similar for all fatty acids and 3-fold higher than in the experiments without skin pretreatment.

Enhanced efficacy by percutaneous absorption of piroxicam from the poloxamer gel in rats

The pharmacokinetics and anti-inflammatory activity of piroxicam from the poloxamer 407 gel were determined to investigate percutaneous absorption of piroxicam from poloxamer gels in rats. The poloxamer 407 gel containing 1% piroxicam showed significant inhibition of carragenin-induced rat foot swelling when compared to the control group. The extent of inhibition of swelling (%) showed a linear relationship with the logarithm of piroxicam dose within ∼0.4–3.2 mg/kg. The enhancing effect of polyoxyethylene-2-oleyl ether, non-ionic surfactant on the percutaneous absorption of piroxicam from poloxamer 407 gel was evaluated in rats. The piroxicam gel containing polyoxyethylene-2-oleyl ether increaesd the relative bioavailability ∼1.8-fold compared with the gel without enhancer. Percutaneous administration of piroxicam gel containing polyoxyethylene-2-oleyl ether to rats showed a relatively constant, sustained blood concentration with minimal fluctuation.

Influence of non-ionic surfactants, pH and propylene glycol on percutaneous absorption of piroxicam from cataplasm

The influence of pH in the formulation, ethylene oxide chain length of polyoxyethylene (POE) non-ionic surfactants and addition of propylene glycol (PG) on percutaneous absorption of piroxicam (Px) from cataplasm was investigated in guinea-pig in vivo. The area under the plasma concentration of Px curve until 8 h after the application (AUC 0–8) increased with increasing the cataplasm base pH up to 6.5 and then plateaued from pH 6.5 to 7.2. Px solubility in water increased markedly with increasing pH from pH 6 as Px is a weak acid and its p K a is 5.3. The ionic form of Px in the cataplasm was suspected to contribute to the percutaneous absorption of Px. The percutaneous absorption of Px from the cataplasms containing 5% of POE non-ionic surfactants with various POE lengths were examined. The parabolic relation between the Px absorption and the POE length was observed. POE length from 5 to 15 enhanced percutaneous absorption to a greater extent. An attempt was also made to examine the influence of the addition of PG to the formulation containing POE (9) lauryl ether. The addition of 20% PG to the formulation significantly increased the Px concentration in plasma, compared to 0, 5, 10 and 15% PG. Skin and cutaneous muscle concentrations significantly increased by addition of 20% PG, compared to those by 0% PG but not in deeper muscle.

Percutaneous Absorption of Piroxicah from Fapg Base Through Rat Skin: Effects of Oleic Acid and Saturated Fatty Acid Added to Fapg Base

AbstractOleic acid (OA) or / and saturated fatty acid (i.e. lauric lyristic, palmitic and stearic acid) decreased the release of piroxican from FAPG (fatty alcohol-propylene glycol) base. The reason would be due to the increase in lipophilicity of the base. The released piroxicam was found to be inversely proportional to the apparent viscosity of the ointments containing OA and saturated fatty acid. However, OA or / and the saturated fatty acids enhanced the in vitro skin permeation and the in vivo percutaneous absorption of piroxican, the enhancing effect was decreased linearly with increasing carbon number of saturated fatty acid from 12 to 18. A useful parameter has been obtained for estimating the properties of the exudation or “bleeding” of the FAPG base. A number of piroxicam FAPG ointments have been selected as an optimal product for less bleeding and more percutaneous absorption of piroxicam than those of controls (containing no oleic acid and saturated fatty acid).

The effect of pretreatment by penetration enhancers on the in vivo percutaneous absorption of piroxicam from its gel form in rabbits

The effects of pretreatment period with 80% dimethyl sulfoxide (DMSO) and 10% oleic acid in propylene glycol (PG) on the percutaneous absorption of piroxicam from its gel form through rabbit abdominal skin were investigated. The area under the curve of plasma piroxicam concentration from 0 to 24 h (AUC 0–24h) for 1 h pretreatment with 10% oleic acid/PG was 8-fold higher than that of nonpretreatment, and was similar to that of 6 or 12 h pretreatment. Compared to the lag time of skin permeation of piroxicam for nonpretreatment (2 h), the lag time for the pretreatments was nearly diminished. The AUC 0–24h value of piroxicam for 24 h pretreatment was about 22-fold higher than that of nonpretreatment, and the absolute bioavailability for 24 h pretreatment was 62%. In contrast to 10% oleic acid/PG, 1 h pretreatment with 80% DMSO/PG had no enhancing effect on the percutaneous absorption of piroxicam from the gels. However, the AUC 0–24h values of piroxicam increased linearly with length of the pretreatment period from 1 to 24 h. Photomicrographs showed that the exfoliation of stratum corneum or epithelium resulted on pretreatment with 10% oleic acid for 18 h.

Effect of lecithin on percutaneous absorption of drugs. II. Mechanism of enhancing effect of lecithin on the percutaneous absorption of indomethacin gel-ointment

The enhancing effect of lecithin (PC) on the percutaneous absorption of drugs in gelointment was investigated. Four hours after a topical application of indomethacin (IM) plus PC-gel-ointment, IM was absorbed through the intact rat back skin and moved into blood, but PC could not be found in the plasma. PC had no effect on the percutaneous absorption of IM through the stripped skin. The pretreatment with the base of gel-ointment containing only PC increased the percutaneous absorption of IM applied as gelointment 4h later. PC inhibited the peroxidation of skin lipids, but did not affect the release of SH group from skin protein. The percutaneous absorption of piroxicam (PX) and diclofenac (DF) was also enhanced by PC. It is suggested from these results that PC has a high affinity with epidermic tissue, changes the fluidity of tissue by hydration of stratum corneum, and enhances the percutaneous absorption of drugs.

Percutaneous absorption of piroxicam from ointment bases in rabbits

In order to investigate the process of percutaneous absorption from various ointment bases, the blood levels of piroxicam were determined at optimal intervals after the ointment application in rabbits. After the oral and intravenous administrations, the plasma levels of piroxicam were described by the two-compartment model. A pharmacokinetic model similar to the percutaneous absorption of indomethacin was developed to test the concepts regarding the percutaneous absorption of piroxicam from topical ointment bases. A reasonably good fit between experimental and calculated values was obtained by taking into account identical absorption rate constant (K a) and the changes in drug release constant (K r) and the fraction of drug absorbed (F). We found that piroxicam in the o/w ointment base (UCH ointment containing 12% propylene glycol) had a better percutaneous absorption effect than the other three different kinds of ointment bases which were a simple ointment, PEG ointment and petrolatum rosewater ointment. The pH value of the water phase in UCH ointment containing 12% propylene glycol was adjusted to pH 9.2 by the sodium bicarbonate-buffered solution, then the percutaneous absorption of piroxicam could be increased. The effect of the amount of piroxicam on the percutaneous absorption was also investigated. The optimal effect with the additives in the ointment was finally attained with an addition of 5% urea.