Ibuprofen Solution Research Articles

Explicit Solvent Molecular Dynamics Simulations of Aβ Peptide Interacting with Ibuprofen Ligands

Using all-atom explicit water model and replica exchange molecular dynamics, we study the interactions between Aβ monomer and nonsteroidal anti-inflammatory drug ibuprofen, which is known to reduce the risk of Alzheimer's disease. Ibuprofen binding to Aβ is largely governed by hydrophobic effect, and its binding site in Aβ peptide is entirely composed of hydrophobic amino acids. Electrostatic interactions between negatively charged ibuprofen ligands and positively charged side chains make a relatively small contribution to binding. This outcome is explained by the competition of ligand-peptide electrostatic interactions with intrapeptide salt bridges. Consistent with the experiments, the S-isomer of ibuprofen binds with stronger affinity to Aβ than the R-isomer. Conformational ensemble of Aβ monomer in ibuprofen solution reveals two structured regions, 19-25 (R1) and 29-35 (R2), composed of turn/helix and helix structure, respectively. The clustering technique and free energy analysis suggest that Aβ conformational ensemble is mainly determined by the formation of Asp23-Lys28 salt bridge and the hydrophobic interactions between R1 and R2. Control simulations of Aβ peptide in ligand-free water show that ibuprofen binding changes Aβ structure by promoting the formation of helix and Asp23-Lys28 salt bridge. Implications of our findings for Aβ amyloidogenesis are discussed.

The effect of formulation vehicles on the in vitro percutaneous permeation of ibuprofen

BackgroundThe transdermal application of substances represents an elegant approach to overcome side effects related to injections or oral treatment. Due to benefits like a constant plasma level, no pain during application and a simple therapeutic regime, the optimization of formulations for transdermal drug delivery has gained interest in the last decades. Ibuprofen is a non-steroidal anti-inflammatory compound which is nowadays often used transdermally. The objective of this work was to conduct a study on the effect of different 5% ibuprofen containing formulations (Ibutop® cream, Ibutop® gel, and ibuprofen solution in phosphate buffered saline) on the in vitro-percutaneous permeation of ibuprofen through skin to emphasise the importance of the formulation on percutaneous permeation and skin reservoir.MethodsThe permeation experiments were conducted in Franz-type diffusion cells according to OECD guideline 428 with 2 mg/cm2 ibuprofen formulation on each skin sample. Ibuprofen was analysed in the receptor fluid and extracted skin samples by UV-VIS high-performance liquid-chromatography at 238 nm. The plot of the cumulative amount of ibuprofen permeated versus time was employed to calculate the apparent permeability coefficient, the maximum flux and the lagtime, all of which were statistically analysed by One-way ANOVA.ResultsAlthough ibuprofen permeation out of the gel increases rapidly within the first four hours, the cream produced the highest ibuprofen delivery through the skin within 28 hours, followed by the solution and the gel. A significant shorter lagtime was found after gel treatment compared with the cream and the solution. After 28 hours 59% of the applied ibuprofen was found in the receptor fluid of the cream treated samples, 26% in the solution treated samples and 21% in the samples treated with the gel. Fourfold higher ibuprofen reservoirs were found in the solution and gel treated skin samples compared to the cream treated skin samples.ConclusionThe present study demonstrates the importance of the formulation on transdermal drug delivery of ibuprofen and emphasises the differences of drug storage within the skin due to the formulation. Thus, it is a mistaken assumption that formulations comprising the same drug amount are equivalent regarding skin permeability.

Stability of Ibuprofen solutions in normal saline or 5% dextrose in water.

A shortage of the standard medication for treatment of patent ductus arteriosus has necessitated use of parenteral ibuprofen, which is equally efficacious for this indication. The beyond-use date recommended by the manufacturer is very short and has implications for resource allocation and wastage. To evaluate the stability of ibuprofen (undiluted or diluted in either 0.9% sodium chloride [normal saline; NS] or 5% dextrose in water [D5W]) with storage for up to 21 days under refrigeration or at room temperature in glass vials or polypropylene syringes. Six glass vials, each containing undiluted ibuprofen (5 mg/mL), were prepared. In addition, ibuprofen was diluted to 2.5 mg/mL in NS or D5W, and 6 syringes were prepared for each diluent (total of 12 syringes). Finally, 6 extension tubes were each primed with 1 mL of ibuprofen (duplicates of undiluted solution and solutions diluted to 2.5 mg/mL in NS or D5W). Half of the vials, syringes, and tubes were stored under refrigeration (4°C) and the other half at room temperature (23°C). The concentration of ibuprofen was determined by a validated, stability-indicating liquid chromatographic method on study days 0, 1, 2, 3, 6, 8, 10, 13, 17, and 21 for samples stored in vials and syringes, or at time 0, 6, 24, and 30 h for samples stored in tubes. Analysis of variance showed differences in the percentage of ibuprofen remaining due to study day (p < 0.001) and diluent (p < 0.005), but no differences due to concentration (p = 0.06) or temperature (p = 0.12). All solutions of ibuprofen were stable throughout the study period, retaining at least 90% of their initial concentration. Undiluted ibuprofen (5 mg/mL) stored in glass vials and ibuprofen diluted to 2.5 mg/mL with either NS or D5W and stored in polypropylene syringes will retain more than 92% of its initial concentration with storage for up to 14 days at 4°C. A beyond-use date of 14 days would allow for up to 24 h storage at 23°C during this 14-day period. Storage of ibuprofen solutions in extension tubing should not exceed 29 h at 4°C or 17 h at 23°C. Beyond-use dates should be applied only after consideration of US Pharmacopeia Revised General Chapter <797> guidelines for compounding of sterile preparations.

β-TCP porous pellets as an orthopaedic drug delivery system: ibuprofen/carrier physicochemical interactions

Calcium phosphate bone substitute materials can be loaded with active substances for in situ, targeted drug administration. In this study, porous β-TCP pellets were investigated as an anti-inflammatory drug carrier. Porous β-TCP pellets were impregnated with an ethanolic solution of ibuprofen. The effects of contact time and concentration of ibuprofen solution on drug adsorption were studied. The ibuprofen adsorption equilibrium time was found to be one hour. The adsorption isotherms fitted to the Freundlich model, suggesting that the interaction between ibuprofen and β-TCP is weak. The physicochemical characterizations of loaded pellets confirmed that the reversible physisorption of ibuprofen on β-TCP pellets is due to Van der Waals forces, and this property was associated with the 100% ibuprofen release.

Enantiospecific fate of ibuprofen, ketoprofen and naproxen in a laboratory-scale membrane bioreactor

The enantiospecific fate of three common pharmaceuticals was monitored in a laboratory-scale membrane bioreactor (MBR). The MBR was operated with a hydraulic retention time of 24 h and a mixed liquor suspended solids concentration of 8.6–10 g/L. Standard solutions of ibuprofen, ketoprofen and naproxen were dosed into the synthetic feed of the MBR. Influent and permeate samples were then collected for enantiospecific analysis. The individual ( R)- and ( S)-enantiomers of the three pharmaceuticals were derivatised using a chiral derivatizing agent to form pairs of diastereomers, which could then be separated and analysed by gas chromatography–tandem mass spectrometry (GC–MS/MS). Accurate quantitation of individual enantiomers was undertaken by an isotope dilution process. By comparing the total concentration (as the sum of the two enantiomers) in the MBR influent and permeate, ibuprofen, ketoprofen and naproxen concentrations were observed to have been reduced as much as 99%, 43% and 68%, respectively. Furthermore, evidence of enantioselective biodegradation was observed for all three pharmaceuticals. ( S)-Ibuprofen was shown to be preferentially degraded compared to ( R)-ibuprofen with an average decrease in enantiomeric fraction ( EF) from 0.52 to 0.39. In contrast, ( R)-ketoprofen was preferentially degraded compared to ( S)-ketoprofen with a relatively minor increase in EF from 0.52 to 0.63. The use of a relatively pure enantiomeric solution of ( S)-naproxen resulted in a significant change in EF from 0.99 to 0.65. However, this experiment consistently revealed significantly increased concentrations of ( R)-naproxen during MBR treatment. It is hypothesised that the source of this ( R)-naproxen was the enantiomeric inversion of ( S)-naproxen. Such enantiomeric inversion of chiral pharmaceuticals during wastewater treatment processes has not previously been reported.

Preparation and release study of ibuprofen‐loaded porous matrices of a biodegradable poly(ester amide) derived from L‐alanine units

AbstractScaffolds of a biodegradable poly(ester amide) constituted of L‐alanine, sebacic acid, and 1,12‐dodecanediol units (abbreviated as PADAS) were prepared by the compression‐molding/particulate‐leaching method. The influence of the type, size, and percentage of salt on the scaffold porosity and morphology was evaluated. The thermal behavior and crystallinity were also studied for samples obtained under different processing conditions. PADAS scaffolds were not cytotoxic because they showed good cell viability and supported cell growth at a similar ratio to that observed for the biocompatible materials used as a reference. The use of PADAS scaffolds as a drug‐delivery system was also evaluated by the employment of ibuprofen, a drug with well known anti‐inflammatory effects. Different drug‐loading methods were considered, and their influence on the release in a Sörensen's medium was evaluated as well as the influence of the scaffold morphology. A sustained release of ibuprofen could be attained without the production of a negative effect on the cell viability. The release kinetics of samples loaded before melt processing was well described by the combined Higuchi/first‐order model. This allowed the estimation of the diffusion coefficients, which ranged between 3 × 10−14 and 5 × 10−13 m2/s. Samples loaded by immersion in ibuprofen solutions showed a rapid release that could be delayed by the addition of polycaprolactone to the immersion medium (i.e., the release rate decreased from 0.027 to 0.015 h−1). © 2011 Wiley Periodicals, Inc. J Appl Polym Sci, 2011.

Solubilization of ibuprofen with β-cyclodextrin derivatives: Energetic and structural studies

The aim of this work was to investigate the complexation of ibuprofen as model drug with various β-cyclodextrins (native β-cyclodextrin, hydroxypropyl-β-cyclodextrin with two different molar degrees of substitution, and methyl-β-cyclodextrin). Solutions of the commercially available β-cyclodextrins were prepared in phosphate buffer (73 mM). The pH value was adjusted to 7.4 and the solutions were isotonized with NaCl. A solution of ibuprofen was prepared in the same way. A thermal activity monitor was used for isothermal titration calorimetry (ITC). 1H NMR analysis was employed to investigate the structures of the complexes. ITC analysis showed that each type of β-cyclodextrin had its characteristic values of both enthalpy and mass equilibrium constant for the complexation processes with the drug molecules. 1H NMR spectroscopy of the complexes showed through significant differences in chemical shifts that the physical interaction between the cyclodextrins and ibuprofen molecules were also different, probably due to different three-dimensional arrangements of ibuprofen in the cyclodextrin cavity, induced by the different substituents bonded to the glucose rings. These differences were connected to the thermodynamic parameters of the complexes.

Chitosan-functionalized porous silicon optical transducer for the detection ofcarboxylic acid-containing drugs in water

A chitosan/porous silicon biosensing platform for the detection of carboxylic acid-containing drugs in water is prepared and characterized. Parasitic layer-free films of mesoporous silicon are electrochemically etched and functionalized by covalent attachment of chitosan oligomers. The presence of the chitosan species covering the inner and outer surface of the porous silicon films is confirmed by infrared spectroscopy and nitrogen adsorption analysis. The obtained hybrid platform offers both an important porosity, with a higher surface area than the original porous silicon substrate, and an important surface charge, very suitable for sensing charged molecules. Ibuprofen is chosen as a drug model for the sensing experiments in water. Optical interferometry measurements are performed on the chitosan/porous silicon substrate exposed to ibuprofen solutions of various concentrations, and compared to the same experiments performed on a nonfunctionalized porous silicon surface. Results of the sensing experiments show that the presence of chitosan increases the sensitivity of the sensing porous film by more than one order of magnitude compared to the nonfunctionalized porous film. Detection in water of BHB, a model molecule for illicit rape drug GHB, is also demonstrated at concentrations compatible with forensic analysis, using the chitosan/porous silicon hybrid platform.

TLC Chromatographic-Densitometric Assay of Ibuprofen and Its Impurities

A simple and sensitive thin-layer chromatographic (TLC)-densitometric method for the quantitative estimation of S(+)-2-[4-isobutylphenyl]propionic acid (ibuprofen) and its impurities in pharmaceutical preparations has been developed. The chromatographic separation was carried out on silica gel 60 F(254) TLC plates using toluene-ethyl acetate-glacial acetic acid (17:13: 1, v/v/v) as the mobile phase. Detection was carried out densitometrically with a UV detector. The developed method has detection and quantitation limits ranging from 0.13 μg per spot to 0.72 μg per spot. For individual constituents the recovery ranged from 96.8% to 99.0%. In addition, the stability of ibuprofen solutions was investigated, including the effect of pH, temperature, and incubation time. The method is rapid, simple, and suitable for routine quality-control analysis of pharmaceuticals containing ibuprofen.

Ozonation of NSAID: A Biodegradability and Toxicity Study

This work deals with the biodegradability and toxicity of three non-steroidal anti-inflammatory drugs (NSAID) (diclofenac, ibuprofen and naproxen) treated by ozonation. The results show that the total removal of 200 mg L−1 of diclofenac and 100 mg L−1 of naproxen is possible using an ozone dose of 0.20 and 0.04 g L−1, respectively. For 200 mg L−1 of ibuprofen, 90% removal is achieved using an ozone dose of 2.3 g L−1. The BOD5/COD ratio, the Zahn-Wallens test and EC50 toxicity test (Microtox) are chosen as biological and toxicity indicators of NSAID intermediates. The evolution of BOD5/COD ratio during 1 hour of treatment is evaluated and the results show that ozonation improves the biodegradability for the three NSAID treated solution. The Zahn-Wellens test for diclofenac and ibuprofen solutions shows that biological mineralization, after 28 days, is higher for diclofenac than for ibuprofen solution. According to the Microtox test, the treatment with ozone removes the toxicity of the naproxen solution. Taking into account the results obtained with the biocompatibility tests it could be assumed that ozonation is an adequate treatment for removal NSAID in aquatic medium, and the ozonated effluents could be post-treated in a biological wastewater facility.

Composite microparticles with in vivo reduction of the burst release effect

The aim of this study was to develop microparticles containing nanoparticles (composite microparticles) for prolonged drug delivery with reduced burst effect in vitro and in vivo. Such composite microparticles were prepared with hydrophobic and biodegradable polymers [poly(ε-caprolactone), poly(lactic-co-glycolic) acid]. Ibuprofen was chosen as the model drug, and microparticles were prepared by the extraction technique with ethyl acetate as the solvent. Nanoparticles and microparticles and an ibuprofen solution (Pedea ®) were administered subcutaneously at the dose of 1 mg of ibuprofen per kg to overnight-fasted rats (male Wistar). Composite microparticles showed prolonged ibuprofen release and less burst effect when compared to simple microparticles (without nanoparticles inside) or nanoparticles both in vitro (PBS buffer) and in vivo. Moreover, ibuprofen was still detected in the plasma after 96 h with composite microparticles. Consequently, it has been demonstrated that composite microparticles were able to reduce burst release and prolong the release of ibuprofen for a long period of time.

Degradation of the emerging contaminant ibuprofen in water by photo-Fenton

In this study the degradation of the worldwide Non-Steroidal Anti-Inflammatory Drug (NSAID) ibuprofen (IBP) by photo-Fenton reaction by use of solar artificial irradiation was carried out. Non-photocatalytic experiments (complex formation, photolysis and UV/Vis-H 2O 2 oxidation) were executed to evaluate the isolated effects and additional differentiated degradation pathways of IBP. The solar photolysis cleavage of H 2O 2 generates hydroxylated-IBP byproducts without mineralization. Fenton reaction, however promotes hydroxylation with a 10% contamination in form of a mineralization. In contrast photo-Fenton in addition promotes the decarboxylation of IBP and its total depletion is observed. In absence of H 2O 2 a decrease of IBP was observed in the Fe(II)/UV–Vis process due to the complex formation between iron and the IBP-carboxylic moiety. The degradation pathway can be described as an interconnected and successive principal decarboxylation and hydroxylation steps. TOC depletion of 40% was observed in photo-Fenton degradation. The iron-IBP binding was the key-point of the decarboxylation pathway. Both decarboxylation and hydroxylation mechanisms, as individual or parallel process are responsible for IBP removal in Fenton and photo-Fenton systems. An increase in the biodegradability of the final effluent after photo-Fenton treatment was observed. Final BOD 5 of 25 mg L −1 was reached in contrast to the initial BOD 5 shown by the untreated IBP solution (BOD 5 < 1 mg L −1). The increase in the biodegradability of the photo-Fenton degradation byproducts opens the possibility for a complete remediation with a final post-biological treatment.

In vitro Chiral Conversion, Phase Separation, and Wave Propagation in Aged Profen Solutions

We have shown, earlier, that profens, i.e., 2-arylpropionic acids can undergo oscillatory in vitro chiral conversion, exhibiting oscillatory changes in the chromatographic retention parameter (R F) and the specific rotation ([α]D) for periods of up to two weeks after preparation of the solutions in aqueous ethanol. Here, we examine the oscillatory chiral conversion of S-(+)-ibuprofen and S,R-(±)-ketoprofen dissolved in 70% aqueous ethanol and stored in tightly closed colorless glass vials for one year. During that time, each initially homogenous, transparent profen solution separates into two immiscible layers, one clear and the other turbid. Employing chiral thin layer chromatography, high performance liquid chromatography with diode-array detection, gas chromatography, and Raman spectroscopy, we find that both samples undergo chiral conversion to yield a strong predominance of the R-(−) antimer. Additionally, microscopy reveals characteristic spatial patterns in both layers of the demixed ibuprofen and ketoprofen solutions. We use a model proposed earlier for the homogeneous oscillatory interconversion of the S and R profens involving two linked templators to simulate microscopic spatial patterns analogous to those observed in the solutions investigated here.

Self-Assembly of Ibuprofen and Bovine Serum Albumin−Dextran Conjugates Leading to Effective Loading of the Drug

A simple and green process of simultaneous formation of albumin nanoparticles and encapsulation of hydrophobic drugs in aqueous solution was developed. Bovine serum albumin (BSA)-dextran conjugates were prepared through the Maillard reaction. Ibuprofen was used as a drug model. The solubility of protonated ibuprofen decreases, and then precipitation occurs when the pH of saturated ibuprofen solution is changed from alkali to acidic value. In the presence of the conjugates, a binding of ibuprofen with BSA through hydrophobic and electrostatic interactions can suppress the precipitation of ibuprofen. After a heat treatment, the gelation of BSA results in the formation of nanoparticles and fixing of the ibuprofen in the core. The nanoparticles were characterized with dynamic and static light scattering, zeta-potential, and transmission electron microscopy. The nanoparticles are of spherical shape having a hydrodynamic diameter of about 70 nm. As much as 0.7 unit weight of ibuprofen can be loaded into one unit weight of the conjugates. The dextran conjugated to BSA stabilizes the nanoparticles in aqueous solution.

Thermal Treating of Acrylic Matrices as a Tool for Controlling Drug Release

The purpose of the present study was to investigate the effect of thermal-treating on the release of ibuprofen from the granules prepared using aqueous dispersions of Eudragit. To accomplish this goal, different formulations were prepared using wet granulation method containing two different types of Eudragit aqueous dispersions, RS30D, RL30D and Avicel as filler. Tablets were prepared using direct compression method. The prepared tablets were thermally treated at 50 and 70 degrees C for 24 h. The drug release from tablets was assessed before and after thermal-treating. The results of release study showed that, thermally-treating the tablets at the temperatures higher than glass transition temperature (Tg) of the polymer can decrease the drug release from matrices. For mechanistic evaluation of the effect of thermal-treating, powder X-ray diffraction (XPD), scanning electron microscopy (SEM), differential scanning calorimeter (DSC), Fourier transform infrared (FT-IR) and helium pycnometer have been employed. The SEM graphs showed that the tablets have smoother surface with less porosity after thermal-treating. FT-IR spectra showed no change in the spectrum of thermally-treated tablet compared to control. In DSC graphs, no crystalline change was seen in the heat-treated samples of ibuprofen tablets, but decreased and widened peak size were related to the probable formation of solid solution of ibuprofen in Eudragit matrix. The results of helium pycnometer showed a significant decrease in the total porosity of some heat-treated samples. This study revealed the importance of thermal treating on the drug release from sustained release tablets containing Eudragit polymer.

Non-steroid anti-inflammatory drugs in the treatment of patent ductus arteriosus in European newborns

Introduction. Patent ductus arteriosus (PDA) is a common cause of morbidity and mortality among very low birth weight infants and must be treated on an individual basis. Non-steroid anti-inflammatory drugs (NSAIDs) have been used in the treatment of PDA. However, no general guidelines have been followed.Aim. To know the European reality on NSAIDs in the treatment of PDA in preterm newborns.Methods. A questionnaire was sent to 24 European Societies of Neonatology and Perinatology to be filled, at least, by two neonatal intensive care units (NICUs) in each country, and to three representatives NICUs in Europe.Results. We received 45 filled forms from 19 countries: 1 (2%) from North, 12 (27%) from East, 6 (13%) from West, and 26 (58%) from South Europe. Intravenous (iv) indomethacin is used in 32 (71%) NICUs (88% use a 30–60 min perfusion), iv ibuprofen in 16 (36%), and oral ibuprofen in 13 (29%). In 45% of NICUs a second course is used; 27% prescribed a third one. Prolonged treatment, 4–6 days, is mentioned by 45% of NICUs, in extremely low birth eight infants and after the failure of 3 courses of treatment. Prophylactic treatment is used in two NICUs, 24% treat no hemodynamically significant PDA, 96% treat with NSAIDs hemodynamically significant PDA and one NICU uses surgical closure as first line treatment. The ibuprofen/indomethacin contra-indications and preferences are similar to the literature. Pedea® is the iv ibuprofen solution used and oral ibuprofen is a solution with 20 mg/ml. The choices are influenced by economical reasons in 22% of NICUs.Conclusion. Our data show a wide variation among NICUs and countries, regarding the use of NSAIDs to treat PDA, and that no general guidelines are followed. Guidelines or recommendations are necessary to standardize treatment of PDA in Europe, in order to give to all newborns identical health care opportunities.

Dermatopharmacokinetics: Factors Influencing Drug Clearance from the Stratum Corneum

The dermatopharmacokinetic methodology, in which tape stripping of the stratum corneum (SC) is used to access the amount of drug accumulated in the skin barrier, has been proposed for the quantification of topical drug bioavailability. This investigation examined the clearance phase of a model drug from the SC after a short application of an infinite dose. A saturated solution of ibuprofen in propylene glycol/water was applied to the forearm of human volunteers for 30 min. The formulation was then removed and the drug profile across the SC was assessed immediately, and over the next 4 h. The clearance phase depends only on drug diffusivity in the SC. However, the expected, progressive "flattening" of the concentration profiles with increasing time post-formulation removal was not observed. It was subsequently deduced, using infrared spectroscopy, that the rapid percutaneous diffusion of propylene glycol, relative to ibuprofen, resulted in the transient maintenance of a saturated drug concentration at the SC surface even after removal of the original formulation. The important role of formulation excipients in topical delivery is demonstrated, and the local disposition of cosolvents within the SC may impact significantly on drug dermatopharmacokinetics and local bioavailability.

Effects of ibuprofen on the viability and proliferation of rainbow trout liver cell lines and potential problems and interactions in effects assessment

Under some conditions ibuprofen was either cytotoxic or cytostatic to rainbow trout cell lines: RTL-W1 (liver) and RTH-149 (hepatoma). Ibuprofen at up to 15 microg/mL was not cytotoxic, regardless of dosing protocols, exposure conditions, viability endpoints, or cell lines. Responses to higher ibuprofen concentrations depended on the test methodology. No cytotoxicity was seen when stock ibuprofen solutions had been prepared in ethanol. For stock solutions in dimethylsulfoxide (DMSO), ibuprofen from 50 to 1500 microg/mL elicited little cytotoxicity in cultures in which the final DMSO concentration was 0.05% (v/v), but was consistently cytotoxic after 24 h for cultures with 0.5% DMSO (v/v). Cytotoxicity was evaluated with alamar Blue (AB) and carboxyfluoroscein diacetate acetoxymethyl ester (CFDA-AM) as measures respectively of metabolic activity and membrane integrity. Effective concentrations (EC50s) for ibuprofen with AB and CFDA-AM depended on whether the stock solution was dosed directly into a culture well or mixed in medium prior to being added to a well. For indirect dosing, ibuprofen was more cytotoxic in medium without fetal bovine serum (FBS), whereas for direct dosing ibuprofen was equally cytotoxic in medium with or without FBS. As judged by AB and CFDA-AM EC50s, dosing ibuprofen was directly 10 to 30 times more cytotoxic. In FBS-containing cultures, which was dosed with increasing ibuprofen and DMSO at 0.05% (v/v), cell proliferation was impaired at 50 and 150 microg/mL ibuprofen. Lipopolysaccharide (LPS) at 50 microg/mL had little influence on these cytotoxic and cytostatic effects of ibuprofen in medium with FBS.

Europium(III)-Sensitized Chemiluminescence Determination of Ibuprofen in Pharmaceutical Preparations and Biological Fluids

Chemiluminescence reaction of the system containing europium(III) ion, KMnO4, Na2SO3, and ibuprofen was investigated for the determination of ibuprofen. The introduction of Eu(III) ion into the system of KMnO4-Na2SO3-ibuprofen caused a significant increase in the chemiluminescence signal. The increment of the chemiluminescence signal is proportional to ibuprofen concentration in the range of 5.0 × 10−8–5.0 × 10−6 g/ml with a detection limit of 1 × 10−8 g/ml. The relative standard deviation for 1.0 × 10−7 g/ml ibuprofen solution was 1.7% (n = 11). The proposed method was successfully applied to determine ibuprofen in tablets and human plasma.

Structure and properties of ibuprofen–hydroxypropyl methylcellulose nanocomposite gel

From a mixture of a methanol solution of ibuprofen (IB) and an aqueous solution of hydroxypropyl methylcellulose (HPMC), clear, uniform sol was obtained at the methanol/water proportion 7/3. When sol was brought to dryness, nanocomposite gel was obtained with amorphous IB particles of 20–50 nm dispersed in HPMC matrix. Simultaneous and quick nano-hybridization and amorphization are based on: (i) re-precipitation of IB in the restricted space of HPMC network, and (ii) recombination of hydrogen bonds from those within IB crystal to those between IB and HPMC. Associated change in the properties including dissolution into aqueous medium was discussed briefly in view of application feasibility to pharmaceutical processing.