Pressure Sensitive Adhesive Matrix Research Articles

Pyrolysis and flammability of phosphorus based flame retardant pressure sensitive adhesives and adhesive tapes

Pressure-sensitive adhesive tapes are used in a variety of applications such as construction, aircrafts, railway vehicles, and ships, where flame retardancy is essential. Especially in these applications, phosphorus-based flame retardants are often chosen over halogenated ones due to their advantages in terms of toxicity. Although there are pressure-sensitive adhesives with phosphorus flame retardants available on the market, their flame-retardant modes of action and mechanisms are not entirely understood. This research article provides fundamental pyrolysis research of three phosphorus-based flame retardants that exhibit different mechanisms in a pressure-sensitive adhesive matrix. The flame-retardants modes of action and mechanisms of a 9,10-dihydro-9-oxa-10-phosphaphenanthrene-10-oxide (DOPO) derivate, an aryl phosphate, and a self-synthesized, covalently bonded DOPO derivate (copolymerized) are investigated. The blended DOPO derivate is volatilized at rather low temperatures while the covalently bonded DOPO derivate decomposes together with the polymer matrix at the same temperature. Both DOPO derivates release PO radicals which are known for their flame inhibition. The aryl phosphate decomposes at higher temperatures, releases small amounts of aryl phosphates into the gas phase, and acts predominantly the condensed phase. The aryl phosphate acts as precursor for phosphoric acid and improves the charring of the pressure sensitive adhesive matrix. All flame retardants enhance the flammability of the adhesives depending on their individual mode of action while the covalently bonded flame retardant additionally improves the mechanical properties at elevated temperatures making it a promising future technology for pressure-sensitive adhesives.

Development of long-acting rivastigmine drug-in-adhesive patch utilizing ion-pair strategy and characterization of controlled release mechanism

The purpose of present study was to develop a long-acting drug-in-adhesive patch of rivastigmine (RVS) to achieve controlled release under high drug loading. Formulation factors including ion-pair, pressure sensitive adhesive (PSA), drug-loading and permeation enhancers were investigated through in vitro skin permeation experiments. Optimized patch was evaluated by pharmacokinetic study. The mechanism of controlled release was studied by FTIR, Raman, DSC, rheology study and molecular modeling. The optimized patch composed of RVS-SA (equal to 30% RVS), 15% POCC as permeation enhancer and AAOH as PSA matrix. The RVS in optimized patch was basically permeated at a uniform rate, and the ratio of the skin permeation amount (2803.38 ± 153.85 μg/cm2) in 72 hours to that of the control group (1000.89 ± 62.45 μg/cm2) was 2.8. The plasma concentration of RVS was stable for 72 hours in vivo (AUCoptimized = 5721.30 ± 1994.87 h ng/mL, MRT0-t = 29.55 ± 2.49 h), and Cmax was significantly controlled. The results of the study on the controlled release mechanism showed that the addition of counter ion formed hydrogen bonds with RVS and PSA respectively, which reduced the fluidity and molecular mobility of PSA, and enhanced the interaction between RVS and PSA, thus achieving the purpose of long-acting effect. In conclusion, long-acting drug-in-adhesive patch of RVS was developed, and provided a new idea for the long term drug delivery of Alzheimer's disease.

Alternative therapy of rheumatoid arthritis with a novel transdermal patch containing Siegesbeckiae Herba extract

Ethnopharmacological relevanceSiegesbeckiae Herba (SiH) is a traditional anti-rheumatic herbal medicine in China. A SiH derived product, Phynova Joint and Muscle Relief Tablets™, has been granted the UK license in 2015. Although transdermal delivery provides better patient compliance and relative constant plasma drug concentration, the feasibility of transdermal delivery of SiH was not clear. Aim of the studyThe aim of the present study was to develop a novel transdermal patch containing SiH extract for alternative therapy of rheumatoid arthritis. Materials and methodsSiH extract containing 48.5% (w/w) of kirenol was prepared from Siegesbeckia pubescens Makino. Then transdermal patches containing SiH extract were prepared by the solvent evaporation technique. The formulation of the transdermal patch was optimized based on the in vitro skin permeation experiment. Finally, the anti-inflammatory and analgesic activity of the optimal patch were evaluated by chronic inflammation model induced by complete Freund's adjuvant (CFA) and writhing model induced by acetic acid, separately. ResultsOleic acid (OA) showed the maximum permeation enhancement effect with the enhancement ratio (ER) values of 3.32. Therefore, OA was used as a permeation enhancer in the transdermal patch. The optimal formulation consisted of SiH extract (10% of the matrix, w/w), OA (10% of the matrix, w/w), DURO–TAK® 87–2287 (pressure sensitive adhesive matrix) and Scotchpak™ 9701 (backing layer). The optimal transdermal patch containing SiH extract significantly reduced the degree of paw swelling and number of writhing in inflammation model and writhing model, respectively. ConclusionsThe developed transdermal patch containing Siegesbeckiae Herba extract showed good anti-inflammatory and analgesic effects, which demonstrated a great potential for alternative therapy of rheumatoid arthritis.

Thermally conductive adhesives from covalent-bonding of reduced graphene oxide to acrylic copolymer

ABSTRACTThis work reports about the enhancement of the thermal conductivity of an acrylic pressure-sensitive adhesive (PSA) with the incorporation of functionalized and reduced graphene oxide (frGO) sheet in the composition. Bifunctional isocyanatoethylmetharcylate (IEMA) was intercalated (so-called ‘functionalization’) to the GO surface mainly at its –COOH sites. The remaining oxygenated groups on the GO surface were reduced by dimethyl hydrazine. The frGO was successfully incorporated into PSA matrix through in-situ polymerization of acrylic monomers and subsequently crosslinked under UV radiation. The conductivity and the peel strength of the PSA were studied as a function of filler content, filler modification (functionalization and/or reduction), UV-radiation dosage and mode of filler insertion (through in-situ polymerization or mechanical mixing). frGO/PSA showed much better properties than the PSA system with bare or IEMA-functionalized unreduced GO. In-situ polymerization was found to be more effective method for frGO insertion. Within the range of filler content (0.0–1.0) wt% and UV-radiation dosages of (400–3000) mJcm−2, the thermal conductivity and peel strength of the acrylic PSA-system under investigation varied in the range of 0.17–1.03 Wm−1K−1 and 2831–299 gf/25 mm. This is the first report on ‘reduced GO covalently bonded to polymer chain in an adhesive-composition’ providing novel idea to make PSA-system with balanced thermal conductivity and peel strength with perspective for application in miniature electronic industries.

Ion-pair formation combined with a penetration enhancer as a dual strategy to improve the transdermal delivery of meloxicam.

The aim of the study was to develop a novel drug-in-adhesive patch for transdermal delivery of meloxicam (MLX). The formulation involved a strategy to combine a chemical enhancer with an ion-pair agent. Diethylamine (DETA) was selected as the counter ion to form the ion-pair agent MLX-DETA. MLX-DETA was characterized by nuclear magnetic resonance spectroscopy (NMR) and Fourier transform infrared spectroscopy (FTIR). The ion-pair lifetime (T life) of MLX-DETA was 164.1μs. The water solubility of MLX-DETA was increased nearly 9.3-fold, compared with that of MLX. Oleic acid (OA) was selected as the chemical enhancer, and the optimized formulation consisted of 5% (w/w) MLX-DETA, 5% (w/w) oleic acid, and DURO-TAK® 87-4098 adhesive as the pressure-sensitive adhesive matrix. The permeation study in vitro showed that both the counter ion and chemical enhancer were effective in improving the skin permeation of MLX. Tissue distribution studies demonstrated that higher accumulation of MLX following application of the MLX-DETA patch to the skin could be obtained in rats compared with the MLX-patch group. In conclusion, to increase the skin absorption and obtain a sustained release for the transdermal delivery of MLX, preparation of a drug-in-adhesive patch by combining an ion pair (MLX-DETA) with a permeation enhancer (OA) is a suitable strategy.

Pressure-sensitive adhesive composites with a hydrophobic form of graphene oxide for enhanced thermal conductivity

Pressure-sensitive adhesive (PSA) composites containing oleylamine functionalized graphene oxide (OA-f-GO) fillers were prepared. The effects of the surface modification of graphene oxide (GO) on the morphology of the PSA composites and on its thermal and adhesive properties were investigated. In contrast to GO fillers, the OA-f-GO fillers were found to be uniformly dispersed in the PSA matrix without any agglomeration and voids. The hydrophobization of GO resulting from the oleylamine functionalization improved the compatibility of the GO sheets with the PSA matrix. The thermal conductivity of the OA-f-GO (5 wt%)/PSA composites at UV energy of 2,000 mJ/cm2 was 55%, 140%, and 300% greater than the thermal conductivities of the OA-f-GO (5 wt%)/PSA composites, GO (5 wt%)/PSA composites, and bare PSA at UV energy of 800 mJ/cm2, respectively. In addition, the higher peel strength of the OA-f-GO/PSA composites compared to that of the GO/PSA composites was explained by the better wetting of hydrophobic OA-f-GO fillers in the PSA matrix.

Development of a drug-in-adhesive patch combining ion pair and chemical enhancer strategy for transdermal delivery of zaltoprofen: pharmacokinetic, pharmacodynamic and in vitro/in vivo correlation evaluation

The aim of the study was to develop a drug-in-adhesive patch system for transdermal delivery of zaltoprofen (ZAL). The formulation was designed in combination with the ion pair and chemical enhancer strategy. Seven organic amines were chosen as counter ions, and the prepared ion pairs were characterized by Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC). The in vivo pharmacokinetic performance of ZAL was studied on rabbits following transdermal and intravenous administration. A deconvolution method was applied to determine the correlation between the in vitro permeation and the in vivo absorption. Acetic acid-induced writhing response was conducted on mice to evaluate the analgesic effect. In vitro permeation results showed that both ion pairs and chemical enhancers were effective in modulating ZAL skin permeation from patches. The enhancement ratio was negatively correlated to the polar surface area (PSA) of counter ions, and was positively correlated to the octanol–water partition coefficient (log Ko/w) of chemical enhancers, respectively. The optimized formulation contained 10% (w/w) ZAL-triethylamine and 10% (w/w) isopropyl myristate, with DURO-TAK® 87-4098 as the pressure sensitive adhesive matrix. Furthermore, the in vitro permeation data were well correlated with the in vivo absorption data. The analgesic effect of the optimized patch was comparable to the commercial indometacin plasters. In conclusion, it was feasible for transdermal delivery of ZAL by the synergistic action of ion pair and chemical enhancer, and the in vitro permeation data were indicative of the in vivo performance for the developed patches.

Development of matrix based transdermal delivery system for ketotifen

The purpose of this study was to investigate the feasibility of developing transdermal drug delivery system for ketotifen used for asthma, allergic conjunctivitis, and rhinitis. The permeation of ketotifen in silicone, polyisobutylene, styrene–butadiene–styrene and acrylic-rubber hybrid and acrylic pressure sensitive adhesive matrix was evaluated. Due to good adhesion force and high permeability, acrylic-rubber hybrid adhesive was chosen. Permeation rate was found to increase linearly as the drug concentration in acrylic-rubber hybrid adhesive increased. However, when the drug concentration was 5 % or more in the matrix, recrystallization of ketotifen was observed. The recrystallization process was not inhibited by crystallization inhibitors tested. Significant increase in flux was obtained using Brij® 30, Crovol® A40, Span® 80 and Lauroglycol® FCC as permeation enhancers.

Drug in adhesive type transdermal matrix systems of ondansetron hydrochloride: optimization of permeation pattern using response surface methodology

The present investigation aims at development of pressure sensitive adhesive (PSA) based drug in adhesive type transdermal systems of ondansetron hydrochloride with higher permeation flux. The effect of mixture of two chemical permeation enhancers (oleic acid and lauric acid diethanolamide); and drug loading dose on the ex vivo human cadaver skin permeation from the transdermal patches has been investigated using a d-optimal combined mixture design. Incorporation of chemical permeation enhancers significantly improved the permeability parameters and it was also found that blend of permeation enhancers is more effective than either permeation enhancer. Criterion of desirability was employed to numerically optimize the transdermal system. Optimized formulation was achieved with 67.5% lauric acid diethanolamide, 32.5% oleic acid and 10% drug loading in an acrylate based PSA matrix. Optimized formulation was found to be nonirritating and safe for dermatological application.

Effect of Ethanolamine Salts and Enhancers on the Percutaneous Absorption of Meloxicam from a Pressure Sensitive Adhesive Matrix

The purpose of this study was to investigate the effect of salt formation on the percutaneous absorption of meloxicam through hairless mouse skin from a pressure sensitive adhesive (PSA) matrix. In addition, the influences of enhancers on the permeation of meloxicam or meloxicam-ethanolamine (MX-EA) salts across the hairless mouse skin were evaluated using a flow-through diffusion cell system. The salt formation of meloxicam resulted in lower permeation rate than the parent drug. 80 provided the highest enhancing effect for meloxicam and meloxicam monoethanolamine salt. The maximum amount of the drug that can be loaded without retarding permeation rate was different depending on the compound. No relationship was found between the fluxes of meloxicam or MX-EA salts from saturated solutions and those from PSA matrices containing the same enhancer.

Enhancement of skin permeation of ketotifen by supersaturation generated by amorphous form of the drug

Pressure sensitive adhesive (PSA) matrices containing amorphous ketotifen were prepared and evaluated for enhanced skin permeability of the drug. A solvent casting method using silicone-typed PSA was employed, and n-hexane, an original solvent for the PSA and one more solvent, dichloromethane, tetrahydrofuran, acetone, ethyl acetate or toluene, were used for complete dissolution of ketotifen and high dispersion in an amorphous state of the drug. Presence of the amorphous form was judged based on the in vitro drug release rate from the matrix. As a result, dichloromethane and tetrahudrofuran were selected as appropriate dilution solvents. In vitro permeation experiments through excised hairless mouse skin revealed that the steady-state flux from the amorphous ketotifen-dispersed matrices was about five times greater than that of the crystalline ketotifen-dispersed matrices, and that the enhancement ratio was in good agreement with the solubility ratio of the amorphous to crystalline form of the drug. Comparison of the skin permeation profiles of amorphous ketotifen-dispersed matrices between two different drug contents suggested that the steady-state flux was not influenced by the drug content. In addition, at both drug contents, the period of the steady-state permeation coincided with the time until the amorphous drug was depleted from the matrix. These results suggest that the increase in skin permeation of ketotifen from PSA matrix was due to the supersaturation generated by amorphous form, and that the amorphous form was stable during the application period.

Transdermal Delivery of Estradiol and Norethindrone Acetate: Effect of Vehicles and Pressure Sensitive Adhesive Matrix

Addition of 30% propylene glycol was required to maintain sink condition in the evaluation of percutaneous absorption of estradiol and norethindrone acetate. The permeability of estradiol was higher in silicone and SIS adhesives. However, estradiol was crystallized in silicone, SIS, and SBS adhesive matrix. The permeability ratio of estradiol or norethindrone acetate from acrylic pressure sensitive adhesives varied widely depending on the functional group of the acrylic adhesives. PEO grafting to acrylic adhesive seemed to change physicochemical property of acrylic adhesive and increased the permeability of estradiol and norethindrone acetate significantly. On the contrary, highly cross-linked enhancer compatible acrylic adhesive decreased the permeability of both estradiol and norethindrone acetate. 20 provided the highest enhancing effect on the permeability of both estradiol and norethindrone acetate followed by oleic acid and EP40. The permeability of the drugs from the developed system was comparable to that from commercial , although significantly lower amount of estradiol and norethindrone acetate were loaded in the developed system.

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 vehicles and pressure sensitive adhesives on the permeation of tacrine across hairless mouse skin

The purpose of this study was to investigate the feasibility of developing transdermal drug delivery (TDD) system for tacrine used for treating the symptoms of Alzheimer’s disease. The effects of various vehicles on the percutaneous absorption of tacrine in solution formulation and in pressure sensitive adhesive (PSA) matrix across the hairless mouse skin were evaluated using flow-through diffusion cell system at 37°C. The permeation profiles of tacrine from solutions were different depending on vehicles used. The flux of tacrine increased significantly as its concentration in the solutions increased. The permeation rate of tacrine was higher in acrylic adhesives with hydroxyl functional group and without functional group than in polyisobutylene adhesive matrix. Incorporation of vehicles into the acrylic adhesive matrix significantly enhanced the permeation rate and shortened the lag time of tacrine. The maximum flux obtained from pressure sensitive adhesive matrix seemed to be high enough to obtain therapeutic effect.

Enhancement of percutaneous absorption of ketoprofen: effect of vehicles and adhesive matrix

The effects of various vehicles on percutaneous absorption of ketoprofen in a solution formulation and in a pressure-sensitive adhesive (PSA) matrix were evaluated. The permeation rate of ketoprofen across hairless mouse skin was evaluated using a flow-through diffusion cell system at 37°C. The solubility of ketoprofen was determined using the equilibrium solubility method. Among tested vehicles, octanol, ethanol, and propylene glycol (PG)/oleyl alcohol (OA) mixture showed the highest flux of 30 μg/cm 2 per h from 5 mg/ml solution. However, it was not possible to demonstrate any correlation between the solubility of ketoprofen and its permeation rate, indicating change in the barrier property of the skin and/or carrier mechanism by vehicles used. When the effects of various vehicles on the percutaneous absorption of ketoprofen from acrylic PSA matrix were evaluated, oleic acid showed a slightly higher flux of 2 μg/cm 2 per h than all other solvents tested. As the concentration of ketoprofen in acrylic PSA matrix increased from 6.3 to 16.7%, the permeation rate also increased almost linearly. The permeation rate of ketoprofen from polyisobutylene (PIB)-type PSA matrix was more than three times higher than that from acrylic PSA matrix.

Release kinetics of indomethacin from pressure sensitive adhesive matrices

Release properties of indomethacin (IDM) from pressure sensitive adhesive (PSA) matrices consisting of styrene-isoprene-styrene block co-polymer to pH 7.4 phosphate buffer solution were investigated and kinetically analyzed. The amount of IDM released was increased with increasing initial concentration of the drug in the PSA matrix. When the drug began to be saturated in the matrix beyond its solubility, no further increase in the released amount was observed. These results could be explained by there being little contribution of the crystalline drug in the PSA matrices to the release. On the other hand, decrease in the thickness of the PSA matrix caused marked increase in the release rate of IDM. The reason might be rapid direct release of the crystalline drug from the PSA surface to the buffer solution, and this was confirmed by scanning electron microscopic observation of the surface. Since these results could not be fully analyzed by T. Higuchi's or W.I. Higuchi's equation, a simple compartment model was designed. This model was adequate to describe all release profiles of IDM from the PSA matrices. Obtained kinetic parameters were consistent with the release mechanism described above.

Release of Clonidine Hydrochloride from Pressure-Sensitive Adhesive Matrices Prepared by Emulsion-Type Acrylate Polymers.

The in vitro release characteristics of a model hydrophilic drug, clonidine hydrochloride, from pressure sensitive adhesive (PSA) matrices prepared by two coating methods, direct coating on a backing layer and transfer coating (coating on a liner layer and transfer of the resulting PSA onto a backing layer), with different drying temperatures were measured and evaluated. Hydrophilic polymer, polyethylene glycol (PEG), hydroxypropyl cellulose (HPC) or polyvinyl pyrrolidone (PVP) was added to the matrices to increase the drug release rate. A lower drying temperature showed a higher release rate. Each polymer increased the release rate compared to control (without polymer). A PSA matrix with HPC showed a low initial burst followed by a prolonged release, whereas those with PEG and PVP exhibited a high initial burst and a subsequent low release rate. The difference in the initial burst was related, to a considerable degree, to the affinity of the matrices against water. It was also related to the amount of drug on the matrix surface. The transfer coating and addition of HPV were useful in suppressing the high initial burst and in maintaining a high sustained release rate of the drug from the PSA matrices.

Mathematical models describing the drug release kinetics from pressure sensitive adhesive matrix

Several mathematical models for facilitating the interpretation of the release data cf lipophilic drugs from highly lipophilic matrices were proposed. Aminopyrine (AMP), ethinylestradiol (EE) and dipropylphthalate (DPP) were used as model drugs, and acrylic type pressure sensitive adhesive (PSA) was used as a model lipophilic matrix. Release experiments were performed using a diffusion cell at 37°C. AMP was completely released from the PSA, whereas only a fraction of EE and DPP loaded was released. There are usually several resistances involved in the diffusion of a drug through the matrix, such as interfacial transfer resistance (R) and transport resistance across the stagnant layer (H) during the drug release process; several equations containing above resistances were therefore developed in the Laplace dimension and used to interpret the obtained release data for the three drugs. Analysis of the results suggested that the stagrant layer could be neglected when using our type of diffusion cell and that the release data of the drugs from the PSA matrix could be interpreted by introducing the interfacial migration resistance and partition coefficient between the matrix and receiver solution into a Fick's diffusion equation.

Diffusion of drugs in acrylic-type pressure-sensitive adhesive matrix. II. Influence of interaction

The release of 16 drugs of different molar volumes and functional groups from acrylic-type pressuresensitive adhesive (PSA) matrices was measured. 2-Ethylhexylacrylate (2-EHA) and acrylic acid (AA) copolymer were used to make the PSA matrix. The diffusion coefficient of drugs in the PSA matrix was calculated from the release data using a nonlinear regression analysis. The relationship between the diffusion coefficient of drugs in the PSA matrix and their physicochemical properties such as molar volume and chemical structure was examined. The diffusion coefficient of drugs in the PSA matrix was affected by their molar volume and by the type of functional group present. The observed diffusion behavior was interpreted by the free-volume theory, following classification by functional group and the interaction evaluated between the drug and PSA carboxyl group. The rank order confirmed from the logarithm of diffusion coefficient vs the drug's molar volume profiles (LogD- Mv profile) could not, however, be sufficiently explained by the electrostatic interaction between the PSA component (carboxyl group ) and the drug with various degrees of dipole moment values. Influence of a drug on the polymer-polymer interaction can be estimated by measuring the effect of the drug's loading on its diffusivity in the PSA matrix. A modified WLF equation was used to obtain the interaction parameter, β. The rank order of intensity of the interaction by the model drugs lidocaine, ketoprofen, aminopyrine and dipropylphthalate was evaluated by measuring the β value, and was consistent with that obtained from the LogD- Mv profiles. The absorbance of OH stretching arising from the carboxyl group at 4000 to 2000 cm −1 of the PSA without drugs on Fourier transform infrared spectroscopy ( FT-IR ) was increased with an increase in the acrylic acid content in the PSA, while the absorbance was decreased by the addition of dipropylphthalate, ketoprofen and lidocaine. The extent of the decrease was dependent on the drugs. The results obtained from FT-IR measurement also supported the rank order observed in the diffusion study. A series of these results appeared to indicate that detailed evaluation of interactions such as polymerpolymer, polymer-drug and drug-drug were required for the exact analysis of a drug's diffusion behavior through the polymer matrix (PSA).

Design and evaluation of transdermal flufenamic acid delivery system

AbstractMonolithic-type transdermal flufenamic acid (FA) delivery systems were prepared using an acrylate pressure sensitive adhesive (PSA) which contained 3, 6 and 9% (w/w) of FA. The in vitro release profiles of these systems were examined using modified Franz diffusion cells and observed that FA is molecularly dissolved in the acrylate PSA matrix and the drug released via a solution-diffusion mechanism. Permeation studies through excised hairless mouse skin revealed that the system containing 9% of FA showed the highest flux. The 9% system was further evaluated for its anti-inflammatory effect by applying the system on carrageenan-induced paw edema in mice and concluded that significant inhibition of swelling was produced as compared to the placebo system.