Amount Of Ketoprofen Research Articles

PREPARATION AND IN VITRO EVALUATION OF SELF-NANO EMULSIFYING DRUG DELIVERY SYSTEMS OF KETOPROFEN

Objective: The aim of this study was to formulate, evaluate and characterise nanoemulsion formulation containing a lipophilic drug, Ketoprofen. Methods: Nanoemulsion formulations composed of oil, surfactant, co-surfactants and Ketoprofen were prepared. In all formulations, the percent of surfactants, as well as oil, was varied while the amount of Ketoprofen kept constant. Solubility studies were conducted to select the oil, surfactant and cosurfactant. Phase diagrams were constructed using the aqueous phase titration method. Formulations were selected from the phase diagrams. The prepared nanoemulsions were subjected to different thermodynamic stability tests. Results: Following optimization, the F7 formula (10% oil, 3:1 surfactant to co-surfactant) was thermodynamically stable, with a droplet size of 105 nm and a zeta potential of-26.21 mV. In vitro release study showed that the drug release pattern from formulations F5, F6, F7, F8, F9 and F10 was higher than that of F1, F2, F3 and F4. Conclusion: The present work demonstrates that the nanoemulsion is a promising drug delivery system approach for the enhancement of solubility and dissolution rate of Ketoprofen.

Formulation, preparation and in vitro - in vivo evaluation of compression-coated tablets for the colonic-specific release of ketoprofen

The aim of this study was to formulate and prepare compression-coated tablets for colonic release (CR-tablets), and to evaluate the bioavailability of ketoprofen following the administration of a single dose from mini-tablets with immediate release (IR-tablets) compared to CR-tablets. CR-tablets were prepared based on time-controlled hydroxypropylmethylcellulose K100M inner compression-coating and pH-sensitive Eudragit® L 30D-55 outer film-coating. The clinical bioavailability study consisted of two periods, in which two formulations were administered to 6 volunteers, according to a randomized cross-over design. The apparent cumulative absorption amount of ketoprofen was estimated by plasma profile deconvolution. CR-tablets were able to delay ketoprofen’s release. Compared to IR-tablets used as reference, for the CR-tablets the maximum plasma concentration (Cmax) was lower (4920.33±1626.71 ng/mL vs. 9549.50±2156.12 ng/mL for IR-tablets) and the time needed to reach Cmax (tmax) was 5.33±1.63 h for CR-tablets vs. 1.33±0.88 h for IR-tablets. In vitro-in vivo comparison of the apparent cumulative absorption amount of ketoprofen showed similar values for the two formulations. Therefore, the obtained pharmacokinetic parameters and the in vitro-in vivo comparison demonstrated the reliability of the developed pharmaceutical system and the fact that it is able to avoid the release of ketoprofen in the first part of the digestive tract.

Effects of oxalate and persulfate addition to Electrofenton and Electrofenton-Fenton processes for oxidation of Ketoprofen: Determination of reactive species and mass balance analysis

Electrofenton (EF) has been widely used to remove contaminants from aqueous solution, while Electrofenton-fenton (EFF), is a two stage process that employs partial electrolysis, needs further study. In addition, a combination of oxalate and persulfate with these systems (EF-Oxalate, EFF-Oxalate, EF-Persulfate, and EFF-Persulfate) could improve the oxidation capacity. This study assessed the applicability of these systems for degradation of Ketoprofen as an emerging contaminant. Under batch experiments, results showed that the order of oxidation capacity and mineralization is EF-Persulfate > EFF-Persulfate > EF-Oxalate > EFF-Oxalate > EFF > EF. Radical scavenger experiments indicated that OH is the dominant radical species in EF, EFF, EF-Oxalate, and EFF-Oxalate systems. However, both OH and 1O2 participated in oxidation of Ketoprofen in both EF-Persulfate and EFF-Persulfate processes. Fe(II)/Total Fe ratios in both solution and sludge samples decreased as oxidation capacity enhanced. Solution and sludge analyses revealed that the amount of Ketoprofen and oxidation byproducts increased in sludge over time. Carbon mass balance calculations showed that EF-Persulfate leaves the lowest amount of oxidation by-products in the system. BOD5/COD ratio analyses demonstrated that all studied systems improved biodegradability of the raw wastewater. EFF and EF-Persulfate systems had the lowest and highest operational costs, respectively. Competitive maps were developed to compare all six processes by Ketoprofen removal efficiency, mineralization capacity, and operational costs. Results confirmed that addition of oxalate and persulfate to EF and EFF systems provide good solutions to decrease the load and risk posed by Ketoprofen to water systems.

The role of local anesthesia to reduce pain after PСNL

The goal of the study was to assess the level of postoperative pain in patients undergoing PCNL after paratubal infiltration with local anesthetic to compare this method of anesthesia with a control group where local anesthesia was not provided. 63 patients were included with kidney stones, confirmed by computer tomography (CT), who were planned to undergo percutaneous nephrolithitomy (PСNL). During the observation 6 patients have been excluded in accordance with the exclusion criteria. The remaining 57 patients were randomized into 2 groups: group A (n= 28) at the end of the operation received paratubal infiltration of 0.5% sol. ropivacaine; group B (n= 29) (controls) — local anesthesia was not used. Postoperative pain was assessed by means of VAS-score 1 hour, 6 hours and 24 hours after surgery. Systemic analgesia was performed with NSAIDs (intramuscular injection of 100 mg ketoprofen) when requested by the patient (Patient-Controlled Analgesia). In patients with local anesthesia, the total VAS score evaluated after 1 and 6 hours after the operation was significantly lower than in the control group. The average amount of ketoprofen required for postoperative analgesia in the group of patients with paratubal infiltration was significantly lower than in the control group. Paratubal infiltration of local anesthetic after PCNL significantly reduced postoperative pain and tended to reduce the amount of NSAIDs to eliminate pain, which in turn may reduce the risk of complications associated with NSAID.

Pharmacokinetics and Antiinflammatory Effect of a Novel Gel System Containing Ketoprofen Solid Nanoparticles.

We previously reported that dermal application using nanoparticles improves skin penetration. In this study, we prepared novel topical formulations containing ketoprofen (KET) solid nanoparticles (KETnano gel ointment) and investigated the antiinflammatory effect of the KET nanoparticle formulations on rheumatoid arthritis using adjuvant-induced arthritis (AA) rats. The KETnano gel ointment was prepared using a bead mill method and additives including methylcellulose and Carbopol 934; the mean particle size of the KET nanoparticles was 83 nm. In the in vitro skin penetration experiment, the penetration rate (Jc) and penetration coefficient through the skin (Kp) values of the KETnano gel ointment were significantly higher than those of gel ointment containing KET microparticles (KETmicro gel ointment; mean particle size 7.7 µm). On the other hand, in the in vivo percutaneous absorption experiment, the apparent absorption rate constant (ka) and the areas under the KET concentration-time curve values in the skin of rats receiving the KETnano gel ointment were significantly higher than those of rats receiving the KETmicro gel ointment, and the amounts of KET in the skin tissues of rats receiving the KETnano gel ointment were also significantly higher than those of rats receiving the KETmicro gel ointment. In addition, the application of the KETnano gel ointment attenuated the enhancement of paw edema of the hind feet of AA rats more than the application of the KETmicro gel ointment. Our findings suggest that a topical drug delivery system using nanoparticles could lead to expansion in the therapeutic use of KET.

Vergleichende In-vitro- und In-vivo-Studien zur Permeation und Penetration von Ketoprofen und Ibuprofen an humaner Haut

The aim of the present in vitro and in vivo studies was to compare the permeation and penetration of a 2.5% ketoprofen (CAS 22071-15-4) gel [Phardol Schmerz-Gel (Test-D)] with the permeation and penetration of two other ketoprofen gels (Ref-I, Ref-E) and an ibuprofen (CAS 15687-27-1) gel (Ref-D) on excised human skin. Furthermore, in vivo studies were performed. The permeation studies utilizing static Franz diffusion cells allow the determination of the transdermal (systemic) transport, whereas the penetration studies in vitro (according to the Saarbrücker model) and in vivo permit setting up a concentration-depth profile. For this purpose the permeation kinetics of ketoprofen from three different gels (each containing 2.5% ketoprofen) over a period of two days were determined at heat-separated human skin of different donors. The in vitro permeability coefficients for Test-D (6.50 x 10(-7) cm x s(-1)) and Ref-I (5.72 x 10(-7) cm x s(-1)) were comparable and the transport occurred for both by a factor of 8-9 faster than with Ref-E (0.78 x 10(-7) cm x s(-1)). In parallel to the permeation studies with ketoprofen, the permeability coefficient of caffeine from an ointment was assessed using the skin biopsies of the same donors as a quality assurance. In a second part of the studies, the in vitro penetration of ketoprofen from Test-D was determined over a period of 3 h at three different skin biopsies in comparison to a commercially available 5% ibuprofen gel (Ref-D). As a main result a concentration-depth profile for ketoprofen and ibuprofen could be issued. The ketoprofen (37.7 +/- 12.1 microg/cm2) and the ibuprofen (30.1 +/- 6.0 microg/cm2) penetrate to the same order of magnitude into the upper part of the Stratum corneum, whereas ibuprofen stronger accumulates in the deeper layers (ketoprofen: 27.3 +/- 8.5 microg/cm2; ibuprofen: 73.7 +/- 31.1 microg/cm2). An additional in vivo penetration study was performed with Test-D to set up an in vitro-in vivo (IVIV) correlation. Over a period of 3 h, the amount of ketoprofen in the Stratum corneum in vivo was 78.4 +/- 19.1 microg/cm2 being comparable to the in vitro data.

Characterization of new topical ketoprofen formulations prepared by drug entrapment in solid lipid matrices

This paper describes the evaluation of a new pharmaceutical formulation based on ketoprofen entrapment in a solid lipid particle (SLP) matrix. The drug–SLP samples, which were elaborated using a processing technology based on supercritical CO2, consisted of a model of a controlled‐release system for topical applications. Some of the samples contained silanized TiO2 as an additional ingredient to increase the interaction between drug and lipid matrix. The study of the sample features relied on reversed‐phase high‐performance liquid chromatography with a C18 column and ultraviolet spectroscopic detection at 266 nm. Characterization assays comprised the determination of the overall amount of ketoprofen in the samples, the assessment of the release–permeation kinetic profiles, and the evaluation of impurities and decomposition products. The release and permeation of encapsulated ketoprofen were assayed at 32°C and pH 6.8 by using a static diffusion cell. Results showed a sustained drug delivery for at least 24 h. Besides, no degradation species were detected throughout the release–permeation processes, which indicated that the stability of the drug in the SLP system was preserved. © 2011 Wiley‐Liss, Inc. and the American Pharmacists Association J Pharm Sci 100:4783–4789, 2011

Ketoprofen poly(lactide-co-glycolide) physical interaction

The aim of this work was to provide an understanding of the interaction occurring between ketoprofen and poly(lactic-co-glycolic acid) (PLGA) that leads to polymer plasticization. Experimental glass transition temperature (Tg) values were fitted with the theoretical ones predicted by the Fox and Gordon-Taylor/Kelley-Bueche equations. PLGA films containing different amounts of ketoprofen (KET) were prepared by solvent casting and characterized by scanning electron microscopy, differential scanning calorimetry, and Fourier transform infrared spectroscopy (FTIR). Differential scanning calorimetry evidenced that KET acted as a plasticizer in a similar biphasic way in both end-capped and uncapped PLGA. At KET contents of 20% to 35%, depending on the investigated polymer, the Tg was around 23 degrees C. Higher KET amounts did not lower further the Tg, and the excess of drug was found to crystallize into the polymeric matrix. Experimental Tg's deviated negatively from the predicted ones probably because of hydrogen bonding. The FTIR spectra of the films, loaded with different amounts of KET, showed a shift to higher wavenumbers for the peaks at 1697 and 1655 cm(-1) confirming the presence of some interactions, probably hydrogen bonds between the ketoprofen carboxylic group and the PLGA carbonyl groups along the polymer backbone. The hydrogen bonding between KET and PLGA is probably responsible for KET plasticizing effect. KET behaving as a lubricant may disrupt polymer chain-chain interactions, removing additional barriers to bond rotation and chain mobility.

관류 랫드 장관모델에서의 케토프로펜의 흡수기전 연구

The aim of this study was to investigate the absorption properties of ketoprofen. The in-situ perfusion model has advantages over in vitro models as it provides intact lymphatic and blood flow circulation. The absorption properties of six different concentrations of ketoprofen have been studied in single pass in-situ rat intestine model. 4000 was used as a permeability marker and the possibility of an energy dependent contribution to ketoprofen absorption was also Investigated using the metabolic inhibitor sodium azide. Three different concentrations of sodium azide were studied to examine its effect on absorption of ketoprofen from the rat intestine. The findings of this study suggest that mono-carboxylic type drugs like ketoprofen cause permeability changes in the intestine. This is shown by the increase in absorption of 4000 as the concentration of ketoprofen is increased. However, the trend for ketoprofen permeability is to decrease over the concentration ranges. It was observed that the Papp values for ketoprofen with sodium azide shows a trend towards reduction in the amount of ketoprofen absorbed from the rat intestine which was significantly different (p by the buffering capacity of the small intestine secretions. The results suggest that mechanisms other than passive diffusion may be involved in ketoprofen absorption. This would be consistent with the involvement of active transport or saturatable processes in the absorption of drugs containing monocarboxylic acid group, as has been previously suggested from in vitro data.

Effect of Formulation Variables on the Percutaneous Permeation of Ketoprofen from Gel Formulations

The objectives of our study were to evaluate the effect of four terpene enhancers, enhancer lipophilicity, and ethanol concentration using hydroxypropyl cellulose (HPC) and two Pluronic F-127 (PF-127) gel formulations on the percutaneous permeation of ketoprofen. All experiments were conducted using hairless mouse skin in vitro. Data recorded over 24 hr was compared with that for control gels (containing no terpene) using Franz diffusion cells. In the three gel formulations, the highest increase in the ketoprofen permeation was observed using limonene followed by nerolidol, fenchone, and thymol. Relationships were established between terpene lipophilicity, enhancement ratios for ketoprofen flux (ERflux), and the cumulative amount of ketoprofen after 24 hr (Q24

Stereoselective drug release from ketoprofen and ricobendazole matrix tablets.

Crystalline characteristics of racemic, pure R and S enantiomers and physical mixtures of Ketoprofen (KET) have been studied by DSC and X-ray diffractometry. Aqueous solubilities were 182.6 +/- 9.1 microg/ml for racemic KET, 259.6 +/- 6.6 microg/ml for R-KET, and 304.3 +/- 2.7 microg/ml for S-KET. Matrix tablets made with racemic and physical mixtures of KET show stereoselective drug release, which is faster for S-KET than for R-KET. This effect is more marked when the chiral excipient hydroxypropylmethylcellulose (HPMC) is used in place of the achiral Eudragit RL. Stereoselectivity of release is also affected by the amount of KET. Similar results were obtained when another chiral drug with low solubility, Ricobendazole (RBZ), is used. Depending on the excipient and drug dosage, more or less marked stereoselective drug release is obtained in RBZ matrix tablet formulations.

Stereoselective drug release from Ketoprofen and Ricobendazole matrix tablets

Crystalline characteristics of racemic, pure R and S enantiomers and physical mixtures of Ketoprofen (KET) have been studied by DSC and X-ray diffractometry. Aqueous solubilities were 182.6 ± 9.1 μg/ml for racemic KET, 259.6 ± 6.6 μg/ml for R-KET, and 304.3 ± 2.7 μg/ml for S-KET. Matrix tablets made with racemic and physical mixtures of KET show stereoselective drug release, which is faster for S-KET than for R-KET. This effect is more marked when the chiral excipient hydroxypropylmethylcellulose (HPMC) is used in place of the achiral Eudragit RL. Stereoselectivity of release is also affected by the amount of KET. Similar results were obtained when another chiral drug with low solubility, Ricobendazole (RBZ), is used. Depending on the excipient and drug dosage, more or less marked stereoselective drug release is obtained in RBZ matrix tablet formulations. Chirality 11:611–615, 1999. © 1999 Wiley-Liss, Inc.