IBU Concentrations Research Articles

The impacts of roller compaction on the quality attributes of simultaneously compressed micro and minitablets

The challenges of developing good quality low dose minitablets was assessed by systematically studying the effects of ibuprofen (IBU, a model compound) particle sizes (6–58 µm D50) and concentrations (0.1–3 %w/w), roller compaction forces (3–7 kN/cm), and the minitablet sizes (1.2, 1.5 and 2 mm diameter). A novel compression approach, where all three minitablet sizes were simultaneously produced in a single compression run was used. Roller compacted ribbons, granules, minitablets were characterized for physico-mechanical properties and minitablets were also characterized for stratified content uniformity and weight uniformity. The results showed that roll force was the more dominant factor to ribbon solid fraction or tensile strength and granule size enlargement. Minitablets obtained from the granules had good weight uniformity; all but one batch met the <Ph. Eur. 2.9.5 > criteria. The precise control of tooling lengths across the various sizes was found profoundly important for achieving expected weights, solid fraction, and tensile strength of the simultaneously produced minitablets. The roller compaction process considerably improved the CU variability of the minitablets as compared to the direct compression process. Smaller particle size and higher concentration of IBU, increased roller compaction force, and larger minitablet size improved the potency and content uniformity; however, only the minitablet size was a statistically significant factor in this study. As a product strategic design criterion, a threshold of 25 minitablets in a dosage unit would ensure robust downstream filling and weight verification operations as well as dose accuracy and uniformity (would pass <USP 905> stage 1 criteria). This study results demonstrated feasibility of the novel simultaneous compression approach and the roller compaction process in developing good quality minitablets.

Removal of Enantiomeric Ibuprofen in a Nanofiltration Membrane Process.

A study of the behavior of R- and S-enantiomers of ibuprofen (R-IBU and S-IBU) in aqueous solution by nanofiltration (NF) membranes revealed that up to 23% of the pharmaceutical was adsorbed onto the stainless steel equipment of a flat-sheet experimental unit. Mass balances disclosed that IBU’s S-enantiomer was primarily responsible for the adsorption onto the equipment. Additional IBU adsorption was also experienced on the NF membrane coupons, verified by increased contact angle measurements on the surfaces. The IBU-equipment adsorptive relationship with and without the membrane coupon were best described by Freundlich and Langmuir isotherms, respectively. At a feed water pH of 4.0 units and racemic µg/L IBU concentrations, NF removal ranged from 34.5% to 49.5%. The rejection of S-IBU was consistently greater than the R-enantiomer. Adsorption onto the surfaces influenced NF rejection by 18.9% to 27.3%. The removal of IBU displayed a direct relationship with an increase in feed water pH. Conversely, the adsorption of IBU exhibited an indirect relationship with an increase in feed water pH.

Seasonal Occurrence of Ibuprofen in Sediment, Water, and Biota in River Owena and Ogbese, and its Ecological Risk Assessment

Abstract The volume of pharmaceuticals discharged into the environment increases daily as a consequence of human life. In the present study, the seasonal variation of ibuprofen in sediment, biota, water, and their exposure risk were investigated in River Owena and Ogbese, Nigeria. The high-performance liquid chromatography coupled to a mass spectrometer (HPLC-MS/MS) was used to analyze the samples after clean up and pre-concentration by solid-phase extraction. The mean concentration of IBU in the samples spanned a range of 1.75 - 2.75 μg/g in sediment, 0.01 – 15.00 μg/g in fish, and 0.00002 – 0.005 μg/ml in water. The measurement of IBU in the sediment and water was significantly elevated in the dry season than the wet season, whereas the opposite was the case in biota. There was a significant interaction between season, media, and rivers with respect to IBU occurrence in the sampled rivers. The calculated bio-water accumulation factor (BWAF) was as high as 750,000 μg/g in fish, proving IBU is extremely bio-accumulative. The ecotoxicological risk assessment for average and worst possible outcome showed that the risk quotient (RQ) for IBU present in the water was sufficient to cause toxicity to fish in both freshwater bodies. The potential bioavailability of IBU to aquatic fauna for prolonged periods spanning several months can result in its circling back into the food web afterward. The baseline info provided by this study in these freshwaters may provide valuable information for the implementation of safety limits for the management of IBU influx into the environment.

Cumulative effects of ibuprofen and air emersion in zebra mussels Dreissena polymorpha

Municipal effluents are major source of pharmaceutical products in the environment. The purpose of this study was to examine the toxicity of a largely used drug, ibuprofen (Ibu), in Dresseina polymorpha mussels and its impact on air survival time. The mussels were exposed to increasing concentration of Ibu (0, 1, 10 and 100μg/L) for 96 at 15°C and a sub-group of mussels was maintain in air for another 96h. Post-exposure mussels (Ibu and Ibu+Air) were analyzed for weight loss, total triglycerides, neutral lipids, lipid peroxidation (LPO), arachidonate-dependent cyclooxygenase (COX) and glutathione S-transferase activity. Lipid extracts of mussel tissues were also analyzed by 1H-nuclear resonance spectroscopy. The data revealed that mussels exposed to Ibu had increased signs of lipid oxidation, neutral lipids and decreased triglycerides, LPO and GST activity. COX activity was significantly reduced by Ibu in keeping with mode of action of the drug. Following exposure to air, increased weight loss, neutral lipids (lipid degradation), were observed in mussels exposed to Ibu but no changes in COX activity were observed. Air stress limited the decrease in triglycerides and the increase in GST in mussels exposed to 100μg/L Ibu indicating decreased anti-oxidant response/phase II biotransformation and limited lipid metabolism. In conclusion, exposure to Ibu has some anti-inflammatory effects to mussels based on COX activity but resulted in increased oxidative damage and lipid catabolism. Exposure to air stress could enhance some of these responses and contribute to decreased resistance to air exposures.

Delivery of ibuprofen by natural macroporous sporopollenin exine capsules extracted from Phoenix dactylifera L.

Sporopollenin macroporous capsules (SMCs) were extracted from date palm (Phoenix dactylifera L.) spores and coated by a natural polymer composite (chitosan with glutaraldehyde). The polymer coated macroporous capsules SMC@poly were used in the in vitro-controlled delivery of ibuprofen. The materials obtained were characterized through spectral, thermal, scanning electron microscopy (SEM), X-ray diffraction (XRD), and nitrogen adsorption–desorption isotherms. The IBU loading and releasing was studied by investigating the changes in various factors such as pH, temperature, and initial concentration. The results revealed that the loading of IBU increased when the concentration of IBU was decreased, following the Langmuir adsorption isotherm. The maximum loading of the IBU was observed at pH6.0 (97.2%, with 50mg/mL). The releasing results indicate that IBU was released faster when the pH was changed from 1.4 to 7.4. In addition, the cytotoxicity of the SMC, SMC@poly, and SMC@poly–IBU were tested against human intestinal Caco-2 cell line using MTT assay, and the results revea'led that all the materials in this study were biocompatible.

Chronic effects induced by ibuprofen on the freshwater bivalve Dreissena polymorpha

The sub-lethal effects induced by the non-steroidal anti-inflammatory drug ((NSAID) ibuprofen (IBU; ((±)-2-(p-isobutylphenyl) propionic acid))) were investigated using a battery of biomarkers on the freshwater bivalve Dreissena polymorpha. According to the results from a semi-static in vivo approach, mussels were exposed for 96 h to increasing levels of environmentally relevant IBU concentrations (0.2, 2 and 8 μg/l, corresponding to 1, 9 and 35 nM, respectively). Cyto-genotoxicity was evaluated via the single cell gel electrophoresis (SCGE) assay, the DNA diffusion assay, the micronucleus test (MN test) and lysosome membrane stability (Neutral Red Retention Assay) in mussel hemocytes. In addition, the activities of catalase (CAT), superoxide dismutase (SOD), glutathione peroxidase (GPx) and the phase II detoxifying enzyme glutathione S-transferase (GST) were measured in the cytosolic fraction that was extracted from a pool of entire bivalves to determine whether the oxidative status was imbalanced. The biomarker battery pointed out a slight cyto-genotoxicity on zebra mussel hemocytes at the IBU concentration of 0.2 μg/l, with higher IBU concentrations able to significantly increase both genetic and cellular damage. In addition, IBU seems to have a considerable effect on the activities of antioxidant and detoxifying enzymes as shown in the exposed specimens' notable oxidative status imbalances.

Infrared microspectroscopy analysis of Ibuprofen release from drug eluting beads in uterine tissue

Ibuprofen loaded embolization beads (IBU-BB) have been developed to reduce inflammation and pain following uterine artery embolization for the treatment of uterine fibroids. The present work has investigated the elution properties of IBU-BB in situ after embolization with Fourier Transform Infrared Microspectroscopy (FTIRMS). Twelve sheep underwent uterine artery embolization with IBU-BB (485 mM) or control unloaded beads. IBU concentration was determined inside the beads and in the tissue surrounding the beads using FTIRMS of uterine tissue sections sampled 24 h or 1 week after embolization. After 24 h, IBU concentration inside the bead was only 18.6 mM out of the 485 mM initially loaded ( p < 0.0001, univariate sign test). The concentration in the tissue around the beads was 8 mM, which is well above the in vitro therapeutic levels (6 µM). After one week the concentration of IBU had decreased to 4.9 mM in the beads ( p = 0.0502, Mann Whitney) and no IBU was detected in the surrounding tissue. This work has demonstrated that IBU-BB can provide a sustained release of the anti-inflammatory drug over at least one week. The in vivo elution properties of IBU-BB may be suitable to alleviate pain and inflammation after embolization.

Metabolites from the biodegradation of pharmaceutical residues of ibuprofen in biofilm reactors and batch experiments.

The three metabolites hydroxyibuprofen (OH-Ibu), carboxyibuprofen (CA-Ibu), and carboxyhydratropic acid (CA-HA), also known from human metabolism of ibuprofen, could be identified in biodegradation experiments. Identification was based on EI mass spectra and comparison with literature data. Detection was performed by selective MS-MS measurements by GC-ion-trap MS and online methylation. Ibuprofen (Ibu), OH-Ibu, and CA-Ibu could be detected with a signal-to-noise ratio of 10:1 at a concentration of 2 nmol L(-1), CA-HA at 0.5 nmol L(-1). Degradation experiments in both biofilm reactors (BFR) and batch experiments with activated sludge (BAS) reveal OH-Ibu as the major metabolite under oxic conditions, and CA-HA under anoxic conditions. CA-Ibu was found under oxic and anoxic conditions almost only in the BAS. The metabolites together do not account for more than 10% of the initial concentration of Ibu.

Spin Trapping of Ibuprofen Radicals: Evidence That Ibuprofen is a Hydroxyl Radical Scavenger

The purpose of this study was to use electron paramagnetic resonance (EPR) spectroscopy to determine if ibuprofen, [2-(4-isobutylphenyl) propanoic acid], a potent nonsterodial anti-inflammatory agent, could modify hydroxyl radicals generation in vitro. Ibuprofen (IBU; 0.1-50 mM) in water or water alone was added to EPR tubes containing ferrous sulfate (0.5-2.0 mM), and either 5,5-dimethyl-1-pyrroline-N-oxide (DMPO; 40 mM) or alpha-phenyl N-tert-butyl nitrone (PBN; 48 mM). Hydrogen peroxide (1 mM) was added to inititate the Fenton reaction, and the systems were then analyzed by EPR spectroscopy to determine the type and relative quantity of free radical(s) produced. IBU caused a dose-dependent decrease of signal intensity of the hydroxyl radical adduct of DMPO (DMPO-OH) which is an indication that IBU either scavenges the hydroxyl radical and/or chelates iron. In addition, other radicals (presumably IBU radicals) produced in these systems were trapped by both DMPO (aN = 16.1 G, aH beta = 24.0 G) and PBN (aN = 15.7 G, aH beta = 4.4 G and aN = 17.0 G, aH beta = 2.1 G). The signal height of these IBU radicals increased in systems containing ferrous sulfate (1 mM), hydrogen peroxide (1 mM), PBN (48 mM), and increasing IBU concentrations. Therefore, we conclude that IBU scavenges the hydroxyl radical. If IBU chelated iron, then less hyroxyl radicals would be generated, less IBU radical formed and the signal height of IBU radicals trapped by PBN would have decreased.(ABSTRACT TRUNCATED AT 250 WORDS)