Skin Permeation Of Ketoprofen Research Articles

Preparation of a Pseudolatex-Membrane for Ketoprofen Transdermal Drug Delivery Systems

Ethyl cellulose (EC) and deproteinized natural rubber latex (DNRL) were used to prepare a pseudolatex-base as a matrix membrane for ketoprofen patches. The pseudolatex-base was prepared using a homogenization and solvent removal method. Either polyvinyl alcohol or polysorbate 80 was used as surfactant and emulsifier. Polyvinyl pyrrolidone, glycerine, isopropyl palmitate, and dibutyl phthalate were used as a channeling agent, skin humectant, enhancer, and plasticizer, respectively. Ketoprofen was incorporated into the pseudolatex-base. All pseudolatex formulations were homogeneous and smooth in texture and elegant in appearance. The pH of pseudolatex formulations was 5–7, and the particle size was 487–787 nm. The viscosity and spreadability test showed the good characteristics of membrane. Stable colloidal dispersion was formed with a zeta potential of −35.18 to −51.55 mV. All pseudolatex formulations were formed into in situ membranes by solvent evaporation in a hot air oven at 70 ± 2 °C. The mechanical test and moisture uptake were characterized, which significantly depended on ingredient. The in vitro release and skin permeation of ketoprofen from the pseudolatex-membrane were evaluated. The suitable pseudolatex-membrane was produced from a EC:DNRL ratio of 1:1 and provided a controlled release and suitable permeation patterns of the ketoprofen. Thus, these systems are essentially based on a matrix membrane made from polymeric pseudolatex systems.

Characterization and skin permeation of ketoprofen-loaded vesicular systems

PurposeTo determine the effect of elasticity on the skin permeation of ketoprofen from surfactant-based vesicular formulations and elastic liposomes. MethodsKetoprofen-loaded surfactant-based vesicles and elastic liposomes were prepared by sonication. Citric buffer (at pH 3.0) was used as rehydration buffer. Characterization studies of the prepared liposomal formulations were performed by dynamic light scattering, extrusion, and 1H and 31P nuclear magnetic resonance (NMR) spectroscopy. Ketoprofen transport studies across human skin were performed for all formulations. ResultsStable ketoprofen-loaded formulations were prepared. Addition of an edge activator, in the absence of the drug, increased the elasticity of the vesicles and liposomes. Ketoprofen loading reduced the elasticity of the liposomes and surfactant-based-vesicles. However, at saturation, the elasticity was still higher than that in the absence of the edge activator and ketoprofen, except for ketoprofen-loaded liposomes with Span 80. NMR studies revealed that the ketoprofen molecules were entrapped in a vesicle bilayer in all vesicular formulations and that the ketoprofen molecules affected the phosphate mobility in the liposomal formulations. Ketoprofen transport studies across human skin clearly showed that the surfactant-based vesicular formulations were superior to the elastic liposomal formulations. ConclusionSurfactant-based vesicles enhance ketoprofen transport across human skin, while no enhancement of ketoprofen was observed when loaded in elastic liposomes.

Development of Ketoprofen Microemulsion for Transdermal Drug Delivery

The aim of this study was to prepare microemulsion for transdermal drug delivery of ketoprofen (KP). The physicochemical and chemical properties of microemulsion were evaluated. The microemulsion were composed of isopropyl myristate (IPM) as oil phase, water, PEG40-hydrogenated castor oil (Cremophor® RH40) as surfactant and PEG400 as co-surfactant, and the surfactant: co-surfactant ratio used was 1:1. The viscosity, droplet size, pH, conductivity of microemulsion and skin permeation of KP through shed snake skin were evaluated. The particle size, viscosity and conductivity of microemulsions were in the range of 172-468 nm, 234.82-1067.35 cP and 6.80-20.87µS/cm, respectively. The ratio of IPM and surfactant mixture played an important role on KP loading capacity of microemulsions formulation and skin permeation of KP. While amount of surfactant increased, the loading capacity of KP increased, but the skin permeation of KP decreased. The results suggested that the novel microemulsion system composed of IPM, water, Cremophor® RH40:PEG400 (ratio 1:1) can be applied for using as a transdermal drug delivery carrier.

Effect of Terpenes on the Skin Permeation of Ketoprofen through Shed Snake Skin

The objective of this work was to investigate the effect of hydrocarbon (a-pinene and limonene) andoxygen containing monoterpenes (carvone and terpineole) at 5%w/v in hydroalcoholic mixtures (50% ethanol)on the permeation of ketoprofen across shed snake skin of Python molurus bivittatus. The amount of KPretained in the skin after 8 h of diffusion was determined. It was found that the percutaneous absorption ofketoprofen was enhanced in the presence of the enhancers. The rank order of enhancement ratio for skinpermeation was found to be a-pinene > limonene > carvone > terpinoele. The enhancers also affected theretention of KP in the skin. The rank order of enhancement ratio for skin retention was the same order with skinpermeation experiment. The results indicated that that lipophilicity is an important structural feature formonoterpenes as skin permeation enhancer for a liphophilic drug, ketoprofen. Key Words: Terpenes; Transdermal delivery; Ketoprofen; Shed snake skin

Transdermal delivery of ketoprofen using microemulsions

A transdermal preparation containing ketoprofen was developed using O/W microemulsion system. Of the oils tested, oleic acid was chosen as the oil phase of the microemulsion, as it showed a good solubilizing capacity and excellent skin permeation rate of the drug. Pseudoternary phase diagrams were constructed to obtain the concentration range of oil, surfactant and cosurfactant for microemulsion formation, and the effect of these additives on skin permeation of ketoprofen was evaluated with excised rat skins. The optimum formulation of the microemulsion consisted of 3% ketoprofen, 6% oleic acid, 30% Labrasol/Cremophor RH 40 (1:1) and water. Terpenes were added to the microemulsion at the level of 5% and their effect on the skin permeation of ketoprofen from the microemulsion was evaluated. Of the four terpenes used, only limonene resulted in a powerful enhancing activity (3-fold increase over control).

Studies on development of pharmaceutical preparation with the purpose of improving controlled-release and bioavailability

During the past fifteen years, the experiments based on three main propositions were proceeded to carry out in our laboratory, that is, (1) Microencapsulation: The method of solvent evaporation in water or oily phases was adopted because of its comparative simplicity in the procedure and its high reproducibility. The application of pharmacokinetic consideration to in vivo evaluation of microencapsulated drugs using beagle dogs intended for obtaining controlled-release by oral administration. The pullulan acetate phthalate microcapsules containing cefadroxil were prepared by the solvent evaporation method in liquid paraffin and showed a zero-order dissolution pattern in pH 6-7.4. (2) Rectal gel preparation: The hydrogels and xerogels were prepared by Eudispert hv. These gels have excellent staying properties in the lower part of the rectum, over a fairly long period. Eudispert hv hydrogels or xerogels containing propentfylline were tested for avoidance of the first-pass metabolism. The absolute bioavailability of propentofylline from gel preparations was almost 100%. (3) Binary vehicle for transdermal delivery: The effects of glycerides, short-chain alcohols and their binary vehicles as donor components on the skin permeation of ketoprofen across the excised hairless mouse skin were evaluated with the diffusion cell. Among single vehicles, Panasate 800 as lipophilic vehicle and ethanol as hydrophilic vehicle showed the effective permeation flux of ketoprofen. The greatest enhancement was observed in an ethanol/Panasate 800 (40/60) binary vehicle. The relationship between lipophilicity and skin permeability of 16 drugs from the ethanol/Panasate 800 (40/60) binary vehicle showed a parabolic shape with a peak at a more hydrophilic range compared with other past references.

Combined effect of d-limonene and temperature on the skin permeation of ketoprofen

The effect of temperature on the enhancement action of d-limonene on percutaneous absorption of ketoprofen (KPF) was investigated in rats in vivo and in vitro. The apparent penetration rate ( R p ) of KPF absorbed from alcoholic hydrogels in rats was estimated based on a pharmacokinetic model, which was derived on the assumption of a constant penetration rate through the skin. The R p value increased sigmoidally with increase in the temperature applied, i.e., the R p value was almost constant at the lower temperatures, however, it increased abruptly at the critical temperature ( T c ) of applied heat. The T c value was significantly lowered by increasing the content of d-limonene in the hydrogel. The steady-state permeability coefficients ( P) of KPF through the skin was determined by employing two-chamber diffusion cells in which the excised rat abdominal skin was mounted. The combined effect of d-limonene and temperature on the P value was also clarified. The Arrhenius plots of P values showed a linear relationship when the skin was pretreated with 30% ethanol without d-limonene. The activation energy of permeation of KPF through the skin was estimated to be 6.49 kJ/mol. When the skin was pretreated with 1.5% d-limonene in 30% ethanol, the Arrhenius plots of P exhibited a convex curvature. Morphological changes of the skin surface were also observed microscopically. The application of heat, along with the synergistic effect of d-limonene, may effectively change the dense barrier structure of the stratum corneum.