Core-shell MOF@COFs used as an adsorbent and matrix for the detection of nonsteroidal anti-inflammatory drugs by MALDI-TOF MS.

A core-shell material (UiO@TapbTp) has been developed as an adsorbent and matrix to detect nonsteroidal anti-inflammatory drugs (NSAIDS) by matrix laser desorption/ionization time-of-flight mass spectrometry (MALDI-TOF MS) in complex samples. The hybrid material is prepared by growing covalent organic framework (COF, TapbTp) layers in situ on an amino-modified metal-organic framework (MOF, UiO-66-NH2). The combination of the MOF and COF overcomes their individual shortcomings and integrates both of their advantages. Compared with the bare COF and MOF, the core-shell composite exhibits improved enrichment ability and matrix performance. With the help of pre-enrichment under optimized conditions, the limits of detection (LODs) for ketoprofen, naproxen, and aspirin are reduced by nearly 1000 times, with values of 0.001 mg L-1, 0.010 mg L-1, and 0.001 mg L-1, respectively, and the relative standard deviations (RSDs) are all below 12.35%. The good recoveries (84.8-118%) in (spiked) saliva and environmental water sample further verify the applicability of the method in complex samples.

Determination of related substances in ketoprofen injection by RP-HPLC method.

The paper aims to establish a RP-HPLC method for the simultaneous determination of six related substances in ketoprofen injection. The separation was performed on a VP-ODS C18 column (4.6mm×250mm, 5µm) with the mobile phase of 6.8% phosphate buffer solution (adjusted to pH3.5 with 85% phosphoric acid)-acetonitrile-water (2:43:55,v/v/v) at a flow rate of 1.2mL•min-1. The detection wavelength and the injection volume were set at 233nm and 20µL, respectively. Impurity A and C were calculated by external standard method. Main component self-compare method with calibration factor was used to calculate impurity B, D, E, F and main component self-compare method without calibration factor was used to calculate unspecified impurity. Related substances and degraded substances were completely separated from ketoprofen. For impurity A and C, the linear range of determination were separately 0.06 µg•mL-1 ~ 3.6µg•mL-1 and 0.036µg•mL-1 ~ 2.4µg•mL-1 with the correlation coefficient of 0.9999. The average recoveries (n=9) were 98.13% (RSD=0.35%) and 96.32% (RSD=0.43%). The precision and repeatability for method were good. With reference to ketoprofen (retention time =10.06 min), the relative retention time of impurity B, D, E, F were 0.71, 1.46, 0.59, 2.13, respectively, and the relative correction factors were 0.962, 0.938, 0.957, 0.960, respectively. Finally, determined that the contents of impurity A could not be more than 0.3%, any of the contents of impurity B, C, D, E, F and unspecified impurities could not be more than 0.2%, sum of the contents of impurities other than A and C couldn't be more than 0.5%. The method was proved to be simple, rapid, accurate, sensitive and suitable for the simultaneous determination of six related substances in ketoprofen injection.

Theoretical and experimental adsorption studies of sulfamethoxazole and ketoprofen on synthesized ionic liquids modified CNTs.

The adsorption of sulfamethoxazole (SMZ) and ketoprofen (KET) using carbon nanotubes (CNTs) and CNTs modified with ionic liquids (ILs) was investigated. Two ionic liquids (1-benzyl, 3-hexyl imidazolium, IL1 and 1-benzyl, 3-decahexyl imidazolium, IL2) were synthesized, and characterized by nuclear magnetic resonance (1H and 13C NMR) and high resolution-mass spectrometry (HR-MS). CNTs and modified CNTs were characterized using FT-IR, X-ray diffraction (XRD), surface area and porosity analysis, thermal gravimetric analysis (TGA), Zeta potential, Raman and scanning electron microscopy (SEM). Kinetics, isotherm and computational studies were carried out to determine the efficiency and adsorption mechanism of SMZ and KET on modified CNTs. A density functional theory (DFT) method was applied to shed more light on the interactions between the pharmaceutical compounds and the adsorbents at the molecular level. The effects of adsorbent dosage, concentration, solution pH, energetics and contact time of SMZ and KET on the adsorption process were investigated. The adsorption of SMZ and KET on CNTs and modified CNTs were pH dependent, and adsorption was best described by pseudo-second-order kinetics and the Freundlich adsorption isotherm. Ionic liquid modified CNTs showed improved adsorption capacities compared to the unmodified ones for both SMZ and KET, which is in line with the computational results showing performance order; CNT+KET/SMZ < CNT-ILs+SMZ < CNT-ILs+KET.

Using chemical benchmarking to determine the persistence of chemicals in a Swedish lake.

It is challenging to measure the persistence of chemicals under field conditions. In this work, two approaches for measuring persistence in the field were compared: the chemical mass balance approach, and a novel chemical benchmarking approach. Ten pharmaceuticals, an X-ray contrast agent, and an artificial sweetener were studied in a Swedish lake. Acesulfame K was selected as a benchmark to quantify persistence using the chemical benchmarking approach. The 95% confidence intervals of the half-life for transformation in the lake system ranged from 780-5700 days for carbamazepine to <1-2 days for ketoprofen. The persistence estimates obtained using the benchmarking approach agreed well with those from the mass balance approach (1-21% difference), indicating that chemical benchmarking can be a valid and useful method to measure the persistence of chemicals under field conditions. Compared to the mass balance approach, the benchmarking approach partially or completely eliminates the need to quantify mass flow of chemicals, so it is particularly advantageous when the quantification of mass flow of chemicals is difficult. Furthermore, the benchmarking approach allows for ready comparison and ranking of the persistence of different chemicals.

Scope of partial least-squares regression applied to the enantiomeric composition determination of ketoprofen from strongly overlapped chromatographic profiles.

Valuable quantitative information could be obtained from strongly overlapped chromatographic profiles of two enantiomers by using proper chemometric methods. Complete separation profiles where the peaks are fully resolved are difficult to achieve in chiral separation methods, and this becomes a particularly severe problem in case that the analyst needs to measure the chiral purity, i.e., when one of the enantiomers is present in the sample in very low concentrations. In this report, we explore the scope of a multivariate chemometric technique based on unfolded partial least-squares regression, as a mathematical tool to solve this quite frequent difficulty. This technique was applied to obtain quantitative results from partially overlapped chromatographic profiles of R- and S-ketoprofen, with different values of enantioresolution factors (from 0.81 down to less than 0.2 resolution units), and also at several different S:R enantiomeric ratios. Enantiomeric purity below 1% was determined with excellent precision even from almost completely overlapped signals. All these assays were tested on the most demanding condition, i.e., when the minor peak elutes immediately after the main peak. The results were validated using univariate calibration of completely resolved profiles and the method applied to the determination of enantiomeric purity of commercial pharmaceuticals.

A dispersive liquid-liquid micellar microextraction for the determination of pharmaceutical compounds in wastewaters using ultra-high-performace liquid chromatography with DAD detection.

A dispersive liquid-liquid micellar microextraction (DLLMME) method coupled with ultra-high-performance liquid chromatography (UHPLC) using Diode Array Detector (DAD) detector was developed for the analysis of five pharmaceutical compounds of different nature in wastewaters. A micellar solution of a surfactant, polidocanol, as extraction solvent (100 µL) and chloroform as dispersive solvent (200 µL) were used to extract and preconcentrate the target analytes. Samples were heated above critical temperature and the cloudy solution was centrifuged. After removing the chloroform, the reduced volume of surfactant was then injected in the UHPLC system. In order to obtain high extraction efficiency, the parameters affecting the liquid-phase microextraction, such as time and temperature extraction, ionic strength and surfactant and organic solvent volume, were optimized using an experimental design. Under the optimized conditions, this procedure allows enrichment factors of up to 47-fold. The detection limit of the method ranged from 0.1 to 2.0 µg/L for the different pharmaceuticals. Relative standard deviations were <26% for all compounds. The procedure was applied to samples from final effluent collected from wastewater treatment plants in Las Palmas de Gran Canaria (Spain), and two compounds were measured at 67 and 113 µg/L in one of them.

Elucidation of transformation pathway of ketoprofen, ibuprofen, and furosemide in surface water and their occurrence in the aqueous environment using UHPLC-QTOF-MS.

The identification and determination of transformation products (TPs) of pharmaceuticals is essential nowadays, in order to track their fate in the aqueous environment and, thus, to estimate the actual pollution. However, this is a challenging task due to the necessity to apply high-resolution instruments enable to detect known and unknown compounds. This work presents the use of liquid chromatography quadrupole time-of-flight mass spectrometry (LC-QTOF-MS) as a powerful tool for the identification of three selected pharmaceuticals, furosemide (FUR), ibuprofen (IBP), and ketoprofen (KET), and their TPs in various water samples. Laboratory degradation experiments were performed using xenon lamp as a source of the irradiation in order to simulate phototransformation processes which may occur in the environment. Furthermore, the photodegradation kinetics of three selected compounds were assessed in a reactor equipped with xenon lamp in river water samples. Five TPs of IBP, seven of KET, and five of FUR were identified; some of them are presented here for the first time. Accurate mass measurements and fragmentation pattern obtained during an LC-QTOF-MS analysis allowed for structure elucidation of TPs followed by the creation of transformation pathway of selected pharmaceuticals. Finally, different water samples (wastewater influent and effluent, river water, untreated and treated water) were analyzed in order to estimate the presence of parent and transformed compounds. Only KET was detected in untransformed form in considered samples. Most of the TPs of selected drugs were found at least once in all water samples. Although IBP and FUR were not present in water samples as parent compounds, their different TPs occur. A great potential of LC-QTOF-MS in the identification and structural elucidation of TPs in the environment, allowing the recognition of the fate of pharmaceuticals in the environment through the determination of transformation pathway, has been presented.

A sensitive enzyme-linked immunosorbent assay amplified by biotin-streptavidin system for detecting non-steroidal anti-inflammatory drug ketoprofen.

A sensitive biotin-streptavidin-amplified enzyme-linked immunosorbent assay (BA-ELISA) method was developed for detecting non-steroidal anti-inflammatory drug ketoprofen. Compared with traditional ELISA method, the sensitivity of proposed immunoassay was enhanced by the biotin-streptavidin system. Under the optimal condition, the median inhibitory concentration (IC50) was 0.25 ng mL(-1), with minor cross-reactivity to a number of structural analogs. This developed assay was successfully applied to detect the ketoprofen residues in different fish samples, and good recoveries (72.6-105.5%) were obtained. The results indicated that this immunoassay method could specifically detect trace ketoprofen residues and could be widely used for routine monitoring of food samples.

Sensing chiral drugs by using CdSe/ZnS nanoparticles capped with N-acetyl-L-cysteine methyl ester.

Chiral quantum dots (QDs), differing in their core or shell size and, consequently, in their optical properties, were synthesized by the treatment of commercially available amine-capped quantum dots with methyl ester N-acetyl-L-cysteine (CysP). Interestingly, their colloidal methanol solutions remain stable for several months. Their NMR and IR spectra were in accordance with CysP binding to the QD surface through two anchoring groups; its thiolate (strongly bound) and the carbonyl group of its ester (weaker bound) group, whereas their circular dichroism (CD) spectra showed a new broad redshifted band, suggesting that the attachment to the QD surface modified the conformational equilibrium towards conformer(s) with optical activity in this region. These QDs were sufficiently fluorescent to perform studies of the chiral recognition of drugs, in particular the aryl propionic acids (APAs) ketoprofen (KP), naproxen (NP), flurbiprofen (FP), and ibuprofen (IP). We used different drug concentration ranges, depending on the QD solubility. All the assayed drugs quenched the QD emission in a concentration-dependent mode. Quenching fluorescence assays with the chiral QDs (CS@CysP) showed their extraordinary capacity for the chiral recognition of KP, NP, and FP, and particularly in the case of KP and FP, a remarkable positive allosteric effect was detected for the R enantiomer. By using a drug/CS@CysP molar ratio of 5000:1 and 2500:1, the changes of intensity and the sign of the CD spectrum of the drug evidenced the dissociation of the drug carboxylic group in the presence of the QD.

In vitro release of ketoprofen from hydrophilic matrix tablets containing cellulose polymer mixtures.

The effect of cellulose ether polymer mixtures, containing both hydroxypropylcellulose (HPC) and hydroxypropylmethylcellulose (HPMC K15M or K100M), on ketoprofen (KTP) release from matrix tablets was investigated. In order to evaluate the compatibility between the matrix components, Raman spectroscopy, scanning electron microscopy (SEM), and X-ray powder diffraction (XRPD) experiments were performed. The results evidence the absence of significant intermolecular interactions that could eventually lead to an incompatibility between the drug and the different excipients. Formulations containing mixtures of polymers with both low and high viscosity grades were prepared by a direct compression method, by varying the polymer/polymer (w/w) ratio while keeping the drug amount incorporated in the solid dispersion constant (200 mg). The hardness values of different matrices were found within the range 113.8 to 154.9 N. HPLC analysis showed a drug content recovery between 99.3 and 102.1%, indicating that no KTP degradation occurred during the preparation process. All formulations attained a high hydration degree after the first hour, which is essential to allow the gel layer formation prior to tablet dissolution. Independent-model dissolution parameters such as t(10%) and t(50%) dissolution times, dissolution efficiency (DE), mean dissolution time (MDT), and area under curve (AUC) were calculated for all formulations. Zero-order, first-order, Higuchi, and Korsmeyer-Peppas kinetic models were employed to interpret the dissolution profiles: a predominantly Fickian diffusion release mechanism was obtained - with Korsmeyer-Peppas exponent values ranging from 0.216 to 0.555. The incorporation of HPC was thus found to play an essential role as a release modifier from HPMC containing tablets.

Advanced oxidation and a metrological strategy based on CLC-MS for the removal of pharmaceuticals from pore & surface water.

In this work, it is studied the photolysis, electrolysis, and photo-electrolysis of a mixture of pharmaceutics (sulfadiazine, naproxen, diclofenac, ketoprofen and ibuprofen) contained in two very different types of real water matrices (obtained from surface and porewater reservoirs), trying to clarify the role of the matrix on the degradation of the pollutants. To do this, a new metrological approach was also developed for screening of pharmaceuticals in waters by capillary liquid chromatography mass spectrometry (CLC-MS). This allows the detection at concentrations lower than 10 ng mL-1. Results obtained in the degradation tests demonstrate that inorganic composition of the water matrix directly influences on the efficiency of the drugs removal by the different EAOPs and better degradation results were obtained for experiments carried out with surface water. The most recalcitrant drug studied was ibuprofen for all processes evaluated, while diclofenac and ketoprofen were found to be the easiest drugs for being degraded. Photo-electrolysis was found to be more efficient than photolysis and electrolysis, and the increase in the current density was found to attain a slight improvement in the removal although with an associated huge increase in the energy consumption. The main reaction pathways for each drug and technology were also proposed.

Pharmaceuticals and personal care products (PPCPs) in water, sediment and freshwater mollusks of the Dongting Lake downstream the Three Gorges Dam.

Pharmaceuticals and personal care products (PPCPs) are a group of emerging anthropogenic pollutants. Here we investigated the occurrence and concentrations of 35 typical PPCPs in water, sediment, and freshwater mollusks (Hyriopsis cumingii, Unio douglasiae, Sinanodonta woodiana, Lamprotula leai and Corbicula fluminea) of the Dongting Lake downstream of the Three Gorges Dam. As results, 33 PPCPs were detected in water and sediment of the lake. Ketoprofen (not detected (ND)-292.8 ng/L, mean 91.1 ng/L) and roxithromycin (13.7-141.9 ng/L, mean 30.4 ng/L) were the primary PPCPs measured in lake water, while ibuprofen (ND-105.0 ng/g, mean 30.0 ng/g) and ketoprofen (ND-142.9 ng/g, mean 27.6 ng/g) were dominant in the sediment. Distinct seasonal difference in PPCP compositions was observed in both water and sediment of the Dongting Lake, potentially associated with the water-level fluctuations driven by the Three Gorges Dam operations. Ketoprofen and ibuprofen were also frequently detected in the soft tissues of freshwater mollusks, with concentrations of 42.5-1206.6 and 44.9-992.7 ng/g, respectively. Significant species-specific accumulation characteristics of PPCPs in mollusks were observed, with the highest total contents being reported for Corbicula fluminea (3.18 ± 1.13 µg/g). Moreover, gonads of mollusks were identified as the target organ to accumulate these compounds. Correlation analysis further revealed the strong associations of PPCP concentrations in mollusks with those in water and sediment, suggesting the importance of controlling dissolved and sedimentary bioavailability of PPCPs for ecological risk management in this freshwater lake ecosystems.

Formulation and evaluation of controlled release matrices of ketoprofen and influence of different co-excipients on the release mechanism.

The present work reports the study of different controlled release formulations of ketoprofen, which is a non-steroidal anti-inflammatory drug (NSAID) and like other NSAIDs requires large and frequent daily doses, resulting in severe side effects and non-compliance. To avoid these problems, controlled release matrices were developed using different grades of ethylcellulose polymer with a drug-polymer ratio of 10:3 by the direct compression method. The effect on drug release of partial replacement of lactose by different co-excipients, HPMC K100 M, starch and CMC, was also studied. The tablets were tested for their drug content, weight variation, friability, hardness, thickness and diameter, all these physical properties being within the USP range. The release profile of all formulations containing polymer and co-excipients was compared with a formulation developed without polymer and co-excipients. After a 24-hour release study, it was concluded that formulations containing different grades of ethylcellulose polymer showed prolonged release for 6-18 hours, but the formulation containing the polymer Ethocel standard FP 7 Premium without co-excipient showed controlled release for 24 hours. DSC and FT-IR studies were performed to investigate any incompatibility between drug, polymer and co-excipient but no interaction was found. Different kinetic models were used, such as first order equation, zero order equation, Higuachi equation, Hixon Crowel's equation and Korsmeyer-Peppas to study the release mechanism. The formulations containing co-excipients showed an enhanced release rate.

pH Gradient as a tool for the separation of ionizable analytes in reversed-phase high-performance chromatography.

The aim of this work was to propose a general scheme of optimizing separation of ionizable analytes and to determine conditions of maximal peak compression in pH-gradient reversed-phase high-performance liquid chromatography (RP HPLC). The approximated explicit equation of the linear pH gradient has been developed. It allows predicting retention times for a given organic modifier content, initial value of pH, and the start and steepness of the pH gradient. Also the formula for calculating maximal peak compression is provided. The developed theory was compared with experimental data on the example of a weak acid (ketoprofen) and a weak base (papaverine). Five parameters characterizing analyte retention (log k(w) and S of the ionized and nonionized forms along with pK(a,chrom)) were determined in a series of isocratic experiments carried out at different pH values and with different methanol contents in the eluent. Next, a series of pH gradients of different pH-gradient steepness and of different pH-gradient starting time has been obtained and used to test the validity of our theoretical approach. The conditions of maximal peak width compression have been found. The derived theory was proved to be in a good agreement with the experimental data. The pH-gradient method led to peak compression of up to 0.2, and minimized peak tailing was obtained for the tested analytes. Since the majority of analytical separations are done in an isocratic mode we proposed a means to transfer an isocratic method to a pH-gradient method.

Electrokinetic supercharging focusing in capillary zone electrophoresis of weakly ionizable analytes in environmental and biological samples.

Five non-steroidal anti-inflammatory drugs, naproxen, fenoprofen, ketoprofen, diclofenac and piroxicam, were separated and analyzed by electrokinetic supercharging in CZE. Three different setups of the ITP technique were assayed for the separation and preconcentration of these five non-steroidal anti-inflammatory drugs. For the setup that gave the best results, we evaluated the influence of different parameters on separation and preconcentration efficiency such as sample pH, concentration of the leading stacker, BGE composition, electrokinetic injection time, composition and hydrodynamic injection of the solvent plug and of the terminating stacker. In the selected setup, the BGE (10 mM Na(2)B(4)O(7) + 50 mM NaCl in 10% of MeOH aqueous solution) contained the leading electrolyte while the terminating electrolyte, hydrodynamically injected after the sample (50 mbar x 12 s), was 50 mM of CHES. Prior to sample injection at (700 s at -2 kV) a short plug of MeOH (50 mbar x 3 s) was hydrodynamically injected. The results show that this strategy enhanced detection sensitivity 2000-fold compared with normal hydrodynamic injection, providing detection limits of 0.08 µg/L for standard samples with good repeatability (values of relative standard deviation, %RSD < 1.03%). Method validation with river water samples and human plasma demonstrated good linearity, with detection limits of 0.9 and 2 µg/L for river water samples and human plasma samples, respectively (as well as satisfactory precision in terms of repeatability and reproducibility).

Terbium sensitized luminescence for the determination of ketoprofen in pharmaceutical formulations.

This paper explores an ultra-sensitive luminescence method for the determination of Ketoprofen (KP) in pharmaceutical formulations. The technique is indirect and exploits the luminescence enhancement of terbium (Tb(3+)) by complexation with KP (Tb(3+)-KP), which was monitored at respective excitation and emission wavelengths of lambda(ex) = 258 nm and lambda(em) = 549 nm. The effect of varying the Tb(3+) concentration and using multiple solvents was examined to determine optimal experimental conditions. Maximum sensitization was accomplished in the presence of methanol where the most favourable condition for the formation of the complex was recorded at a level of 1.0 x 10(-5) M of Tb(3+). Under these optimum experimental conditions, linear calibration curve was obtained in the range of 2.8 x 10(-7)-3.1 x 10(-6) M with a detection limit of 8.7 x 10(-8) M. The technique was validated with 'working' reference standards and produced relative standard deviations < 2% indicating that the reproducibility was highly acceptable. The proposed method was successfully applied to assays of KP in pharmaceutical formulations with average recoveries of 92-98%. The results were found to be in good agreement with those obtained by HPLC. The method is highly suited for general applications of this nature.

Adsorption and degradation of ketoprofen in soils.

Ketoprofen, a nonsteroidal anti-inflammatory drug (NSAID), was commonly found in treated wastewater due to its incomplete removal during sewage treatment plant processes. As treated wastewater is increasingly used for landscape irrigation, it is imperative to understand the leaching potential for ketoprofen in receiving soils. In this study, adsorption and degradation experiments were conducted in four U.S. soils with different physicochemical characteristics. Ketoprofen was not strongly adsorbed to the four soils with K(d) values ranging from 1.26 to 8.24 L kg(-1), suggesting its potential to move downward with percolating water. The adsorption was positively related to the soil organic matter (OM) content (R(2) = 0.890). Degradation experiment showed that half-lives (t(1/2)) of ketoprofen were 4.58 d in Arlington sandy loam (ASL, coarse-loamy, mixed, active, thermic Haplic Durixeralfs), 8.04 d in Hanford loamy sand (HLS, coarse-loamy, mixed, superactive, nonacid, thermic Typic Xerorthents), 15.37 d in Imperial silty clay (ISC, fine, semectitc, calcareous, hyperthermic Vertic Torrifluvents), and 27.61 d in Palouse silt loam (PSL) soil (fine-silty, mixed, superactive, mesic Pachic Ultic Haploxerolls), respectively. Degradation of ketoprofen in soils appeared to be influenced by the soil OM content. The prolonged t(1/2) by sterilization indicated that microbial degradation was the dominant pathway for ketoprofen degradation in soils, while photodegradation only contributed a small portion to the ketoprofen degradation. The t(1/2) and K(oc) values were fitted to screening models to predict the leaching potential of ketoprofen in soils. It appeared that relatively high leaching potential of ketoprofen existed in ISC and PSL soils.

Compatibility and stability of binary mixtures of acetaminophen, nefopam, ketoprofen and ketamine in infusion solutions.

BACKGROUND AND OBJECTIVE: Administering various combinations of acetaminophen, ketoprofen, nefopam and ketamine, though sometimes discussed, is expected to provide superior pain relief and reduce opioid analgesic-related side effects. However, some studies have indicated that multimodal analgesia has limited efficacy. We studied the stability of various binary combinations of these four drugs. PATIENTS AND METHODS: The drugs were studied at 25 degrees C. Binary mixtures of acetaminophen, ketoprofen, nefopam and ketamine were produced. Each drug concentration was assessed using a specific high-performance liquid chromatographic technique. Measurements were carried out at T0, +1, +2, +4, +6 and +24 h. A 5% loss of initial concentration was considered to be significant. The changes with time of the concentrations were analysed using linear regression analysis. A P value of less than 0.05 was significant. RESULTS: The four drugs tested in the binary mixtures were stable, showing neither loss of concentration nor degradation products (P > or = 0.05). CONCLUSION: Physicochemical negative interaction is not likely to account for the limited clinical efficacy sometimes reported with binary combinations of these drugs. Coadministration of binary mixtures of acetaminophen, nefopam, ketoprofen and ketamine from the same bottle or infusion bag using the same venous line is demonstrated to be feasible.

Bio-dis and the paddle dissolution apparatuses applied to the release characterization of ketoprofen from hypromellose matrices.

The purposes of this work were: (1) to comparatively evaluate the effects of hypromellose viscosity grade and content on ketoprofen release from matrix tablets, using Bio-Dis and the paddle apparatuses, (2) to investigate the influence of the pH of the dissolution medium on drug release. Furthermore, since direct compression had not shown to be appropriate to obtain the matrices under study, it was also an objective (3) to evaluate the impact of granulation on drug release process. Six formulations of ketoprofen matrix tablets were obtained by compression, with or without previous granulation, varying the content and viscosity grade of hypromellose. Dissolution tests were carried out at a fixed pH, in each experiment, with the paddle method (pH 4.5, 6.0, 6.8, or 7.2), while a pH gradient was used in Bio-Dis (pH 1.2 to 7.2). The higher the hypromellose viscosity grade and content were, the lower the amount of ketoprofen released was in both apparatuses, the content effect being more expressive. Drug dissolution enhanced with the increase of the pH of the medium due to its pH-dependent solubility. Granulation caused an increase in drug dissolution and modified the mechanism of the release process.

Spectrophotometric determination of ketoprofen and its application in pharmaceutical analysis.

A new simple rapid and sensitive spectrophotometric method has been developed for the determination of ketoprofen in pharmaceutical preparations. The method is based on the reaction of ketoprofen with an analytical reagent--Astra Phloxin FF--at pH 8.0-10.8 and followed by the extraction of formed ion associate in toluene with spectrophotometric detection (it has an absorption maximum at 563 nm, epsilon = 7.6 x 10(4) L x mol(-1) x cm(-1)). The calibration plot was linear from 0.8-16.0 microg x mL(-1) of ketoprofen, and the detection limit was 0.037 microg x mL(-1).