Controlled delivery of ibuprofen from poly(vinyl alcohol)-poly(ethylene glycol) interpenetrating polymeric network hydrogels

Hydrogels composed of poly(vinyl alcohol)(PVA) and poly(ethylene glycol)(PEG) were synthesized using glutaraldehyde as crosslinker and investigated for controlled delivery of the common anti-inflammatory drug, ibuprofen(IBF). To regulate the drug delivery, solid inclusion complexes(ICs) of IBF in β–cyclodextrin(β–CD) were prepared and added to the hydrogels. The ICs were prepared by the microwave irradiation method, which is more environmentally benign. The formation of IC was confirmed by various analytical techniques and the synthesized hydrogels were also characterized. Controlled release of drug was achieved from the hydrogels containing the ICs in comparison to the rapid release from hydrogels containing free IBF.The preliminary kinetic analysis emphasized the crucial role of β–CD in the drug release process that influences the polymer relaxation, thereby leading to prolonged release. The cytotoxicity assay validated the hydrogels as non-toxic in nature and hence can be utilized for controlled delivery of IBF.

Optimization of taste-masking on ibuprofen microspheres with selected structure features

The microsphere was a primary particulate system for taste-masking with unique structural features defined by production process. In this article, ibuprofen lipid microspheres of octadecanol and glycerin monostearate were prepared to mask the undesirable taste of ibuprofen via three kinds of spray congealing processes, namely, air-cooling, water-cooling and citric acid solution-cooling. The stereoscopic and internal structures of ibuprofen microspheres were quantitatively analyzed by synchrotron radiation X-ray micro-computed tomography(SR-μCT) to establish the relationship between the preparation process and microsphere architectures. It was found that the microstructure and morphology of the microspheres were significantly influenced by preparation processes as the primary factors to determine the release profiles and taste-masking effects. The sphericity of ibuprofen microspheres congealed in citric acid solution was higher than that of other two and its morphology was more regular than that being congealed in air or distilled water, and the contact angles between congealing media and melted ibuprofen in octadecanol and glycerin monostearate well demonstrated the structure differences among microspheres of three processes which controlled the release characteristics of the microspheres. The structure parameters like porosity, sphericity, and radius ratio from quantitative analysis were correlated well with drug release behaviors. The results demonstrated that the exterior morphology and internal structure of microspheres had considerable influences on the drug release behaviors as well as taste-masking effects.

Preparation and Crystal Modification of Ibuprofen-Loaded Solid Lipid Microparticles

An emulsion-congealing technique is used to prepare solid lipid microparticles （SLM） containing ibuprofen with glyceryl behenate, tripalmitin and beewax as excipients. The difference of the solubility parameters between the excipients and ibuprofen are used to analyze their compatibility. Both the solubility parameter analysis and the experimental results show that glyceryl behenate is the best among the three excipients. The solid particles disperse well in aqueous phase when the drug loading reaches 10% （relative to lipid only）. Glycerides exhibit marked polymorphism and their rapid rates of crystallization accelerate the formation of metastable crystal modification. The metastable crystal modification characterizes high drug loading capacity but less stability. Increasing the content of lipophilic drug in a lipid matrix facilitates the transformation of excipients to more stable polymorphic forms.

Enhancement of UV-assisted TiO_2 degradation of ibuprofen using Fenton hybrid process at circumneutral pH

A synergistic UV/TiO2/Fenton(PCF)process is investigated for the degradation of ibuprofen(IBP)at circumneutral pH.The IBP decay in the PCF process is much faster than that with the conventional UV,UV/H2O2,Fenton,photo‐Fenton,and photocatalysis processes.The kinetics analysis showed that the IBP decay follows a two‐stage pseudo‐first order profile,that is,a fast IBP decay(k1)followed by a slow decay(k2).The effects of various parameters,including initial pH level,dosage of Fenton’s reagent and TiO2,wavelength of UV irradiation,and initial IBP concentration,are evaluated.The optimum pH level,[Fe2+]0,[Fe2+]0/[H2O2]0 molar ratio,and[TiO2]0 are determined to be approximately 4.22,0.20 mmol/L,1/40,and 1.0 g/L,respectively.The IBP decay at circumneutral pH(i.e.,6.0–8.0 for wastewater)shows the same IBP decay efficiency as that at the optimum pH of 4.22 after 30 min,which suggests that the PCF process is applicable for the treatment of wastewater in the circumneutral pH range.The lnk1 and lnk2 are observed to be linearly correlated to 1/pH0,[IBP]0,[H2O2]0,[H2O2]0/[Fe2+]0 and ln[TiO2]0.Mathematical models are therefore derived to predict the IBP decay.

Chiral Separation of Ibuprofen by Supercritical Fluid Chromatography

The separation method using chiral stationary phase （CSP） for the preparation of enantioselective compound was widely used. In this work, supercritical fluid chromatography（SFC） was proposed to resolve the chiral mixtures. To determine the optimum operating conditions for the chiral separation of the racemic ibuprofen, the retention factors and resolutions with the change in pressure, temperature and the content of IPA （%, by volume） in supercritical CO2 were investigated. Experiments showed that the retention factor decreased with the increase of pressure and decrease in temperature. The retention factor was also influenced by the content of IPA in mobile phase, as the content of IPA in the supercritical fluid increased, the retention factor decreased. The resolution of the enantiomers became worse with the increase of IPA in the supercritical fluid. Through optimizing the experimental conditions, a SFC procedure with 13MPa, 311.15K and 4% IPA in CO2 was obtained. The peak shape of the enantiomers was symmetric with supercritical fluid chromatography when compared to the asymmetric peak shape obtained by the conventional liquid chromatography. This work demonstrated that the developed supercritical fluid chromatography procedure was suitable for the chiral separation of ibuprofen enantiomers.

Resolution of Ibuprofen Ester by Catalytic Antibodies in Water-miscible Organic-solvents

The asymmetric hydrolysis of racemic ibuprofen ester is one of the most important methods for chiral separation of ibuprofen. In this work, a catalytic antibody that accelerates the rate of enantioselective hydrolysis of ibuprofen methyl ester was obtained against an immunogen consisting of tetrahedral phosphonate hapten attached to bovine serum albumin (BSA). The catalytic activity of the catalytic antibody in the water-miscible organic-solvent system composed of a buffer solution and N, N-dimethylformamide (DMF) was studied. With 6% DMF in the buffer solution (containing catalytic antibody 0.25 μmol, 0.2 mol·L-1 phosphate buffer, pH 8) at 37°C for 10 h, a good conversion (48.7%) and high enantiomeric excess (>99%) could be reached. The kinetic analysis of the cata-lytic antibody-catalyzed reaction showed that the hydrolysis in the water-miscible organic-solvent system with DMF in buffer solution followed the Michaelis-Menten kinetics. The catalytic efficiency (Kcat/Km) was enhanced to 151.91 L·mmol-1·min-1, twice as large as that for the buffer solution only.

Simultaneous Quantification of Ibuprofen and Paracetamol in Tablet Formulations Using Transmission Fourier Transform Infrared Spectroscopy

A very simple, non-destructive, inexpensive and green strategy was applied for the simultaneous determination of ibu-profen (IBP) and paracetamol (PC) using transmission Fourier Transform Infrared (FTIR) spectroscopy in tablet formulations for routine quality control laboratories. For the determination of the active pharmaceutical ingredients (API), KBr pellets containing known amount of standards and samples were used for acquisition of the FTIR spectra. The partial least squares (PLS) calibration model was developed using the spectral region from 1781 - 1683 cm-1 for IBP and 1630 - 1530 cm-1 for PC. The excellent coefficients of determination (R2), 0.9999 and 0.9998 were achieved for IBP and PC, respectively. The accuracy of calibration model was also verified through root mean square error of cross validation (RMSECV) which was found to be 0.064. This work clearly shows the capability of transmission FTIR spectroscopy for assessment of exact quantity of API to control the quality of finished products as well as during processing in pharmaceutical industries without involvement of any solvent.

Insights and relative effect of aspirin, naproxen and ibuprofen containing hydrogels: From design to performance as a functional dual capacity restorative material and build in free radical defense: <i>In-vitro</i>studies

Restorative materials in the new era aim to be “bio-active” and long-lasting. It has been suggested that the anti-inflammatory activity of some non-steroidal anti-inflammatory drugs (NSAIDs) may be partly due to their ability to scavenge reactive oxygen species (ROS) and reactive nitrogen species (RNS), as well as to inhibit the respiratory burst of neutrophils triggered by various activating agents. As a part of our continuous interest of developing functional dual action restorative materials capable of being “bio-active” and long-lasting, we design and evaluate novel chitosan hydrogels containing krill oil (antioxidant containing material), naproxen, ibuprofen (non steroidal anti-inflammatory medication), aspirin (pain relieve medication and free radical scavengers) and combinations thereof (chitosan-H-krill oil, chitosan-H-krill oil-aspirin and chitosan-H-naproxen, chitosan-H-naproxen-krill oil, chitosan-H-krill oil-ibuprofen and chitosan-H-ibuprofen) as functional additive prototypes for further development of “dual function restorative materials”;secondly, determine their effect on the dentin bond strength of a composite and thirdly, evaluate the capability of newly designed hydrogels to play an integral role of “build in” free radical defense mechanism by using BSA solubility as a “molecular prototype” of the site of free radical attack in vitro. Materials and Methods: The above mentioned hydrogels were prepared by dispersion of the corresponding component in glycerol and acetic acid with the addition of chitosan gelling agent. The surface morphology (SEM), release behaviors (physiological pH and also in acidic conditions), stability of the therapeutic agent-antioxidant-chitosan and the effect of the hydrogels on the shear bond strength of dentin were also evaluated. Results: The release of aspirin, ibuprofen and naproxen confers the added benefit of synergistic action of a functional therapeutic delivery when comparing the newly designed chitosan-based hydrogel restorative materials to the commercially available products alone. Neither the release of aspirin, ibuprofen or naproxen nor the antioxidant stability was affected by storage over a 6- month period. The hydrogel formulations have a uniform distribution of drug content, homogenous texture and yellow color (SEM study). All chitosan dentin treated hydrogels gave significantly (P < 0.05;non-parametric ANOVA test) higher shear bond values (P < 0.05) than dentin treated or not treated with phosphoric acid. The model protein (BSA) was adopted to evaluate the chitosan-based functional biomaterials as defense for undesired free radical formation under in vitro conditions. Conclusion: The added benefits of the chitosan treated hydrogels involved positive influence on the aspirin, ibuprofen and naproxen release, increased dentin bond strength as well as demonstrated in vitro “build in” free radical defense mechanism, therefore acting as a “proof of concept” for the functional multi-dimentional restorative materials with the build in free radical defense mechanism.

RELEASE OF IBUPROFEN FROM PEG-PLLA ELECTROSPUN FIBERS CONTAINING POLY(ETHYLENE GLYCOL)-b-POLY(α-HYDROXY OCTANOIC ACID) AS AN ADDITIVE

Poly（a-hydroxy octanoic acid） was first used as an additive for the preparation of electrospun ultra-fine fibers of poly（ethylene glycol）-b-poly（L-lactide） （PEG-PLLA）. Ibuprofen was loaded in the electrospun ultra-fine fibers. The results from environmental scanning electron microscopy （ESEM）, wide angle X-ray diffraction （WAXD） and differential scanning calorimetry （DSC） demonstrated that ibuprofen could be perfectly entrapped in the fibers electrospun from PEG-PLLA using a-hydroxy octanoic acid or PEG-b-poly（a-hydroxy octanoic acid） （PEG-PHOA） as additives. Compared with electrospun PEG-PLLA fibers which entrapped 20 wt% ibuprofen, the PEG-PLLA electrospun fibers containing PEG-PHOA exhibited integral and robust after 1 week incubated in 37℃, pH 7.4 phosphate buffer solution with 10 μg/mL proteinase K. Compared with electrospun fibers without PEG-PHOA, the concentration ofproteinase K in release media had less effect on the release rate of ibuprofen. An unique release profile was found from PEG-PLLA fiber after the incorporation of PEG-PHOA. Enzyme degradation experiments demonstrated that PEG-PHOA but not a-hydroxy octanoic acid monomer was the crucial factor for integrity maintenance of the electrospun fibers, which may be due to the enzyme degradation tolerance property of the PEG-PHOA polymer additive.

Design, Synthesis and in vitro Evaluation of Thiazole Derivatives of Ibuprofen as Cyclooxygenase-2 Inhibitors

A series of thiazole derivatives of ibuprofen, as cyclooxygenase-2 Inhibitors, were designed, synthesized and in vitro evaluated.

Effects of Acupressure and Ibuprofen on the Severity of Primary Dysmenorrhea

The present study aims at comparing the effects of acupressure using new combination of acupoints, and Ibuprofen on the severity of primary dysmenorrhea (PD). 216 female high school students, aged between 14 to 18 years, were randomly selected and divided into three groups. Each group underwent different treatment techniques: acupressure, Ibuprofen and sham acupressure as a placebo. The results indicated that the three therapeutic techniques were significantly effective in reducing the pain. However the therapeutic efficacies of acupressure and Ibuprofenwere similar with no significant difference, and were significantly better thanthe placebo. Thus acupressure, with no complications, is recommended as an alternative and also a better choice in the decrease of the severity of PD. ……

Reaction Rate Models for the Thermal Decomposition of Ibuprofen Crystals

Kinetics of the decomposition of racemic ibuprofen crystals were studied by non-isothermal analysis. Thermogravimetric analysis revealed that ibuprofen is thermally stable up to 152.6°C and the initial loss of mass was due to evaporation only. Activation energy, pre-exponential factor, activation entropy and Gibbs free energy for the decomposition of ibuprofen were determined using the integral method of Coats-Redfern (CR). Geometrical contraction models were found to be the best fits. The Arrheinus equation for the thermal decomposition of ibuprofen is k = (1.1 × 107) e–79125/RT sec–1.

Ibuprofen-Maltodextrin Interaction: Study of Enantiomeric Recognition and Complex Characterization

The interaction between ibuprofen and maltodextrins with different dextrose equivalent was studied in solution and solid state in order to investigate the effect on the solubility of ibuprofen and to determine their usefulness in terms of chiral recognition. Apparent binding constants were calculated using nuclear magnetic resonance spectroscopy experiments and solubility studies. The results showed an increase in the apparent solubility of ibuprofen in the presence of maltodextrins that depended on their ionization state. The freeze-drying method was used to prepare solid complexes, while physical mixtures were obtained by simple blending. These solid systems were characterized in the solid state using differential scanning calorimetry, thermogravimetric analysis, Fourier Transform-Infrared spectroscopy, scanning electron microscopy and X-ray diffractometry. Detailed nuclear magnetic resonance studies provided evidence of the influence of the type and concentration of the maltodextrin host on the chiral recognition of racemic ibuprofen, indicating that these linear ligands act as chiral selectors.

A Validated Enantioselective Assay for the Determination of Ibuprofen in Human Plasma Using Ultra Performance Liquid Chromatography with Tandem Mass Spectrometry (UPLC-MS/MS)

A modified ultra performance liquid chromatography-tandem mass spectrometry (UPLC-MS/MS) method was developed and validated for the quantitation of ibuprofen enantiomers in human plasma. Ibuprofen and flurbiprofen (internal standard) were extracted from human plasma at acidic pH, using a single-step liquid-liquid extraction with methyl-tert-butyl ether. The enantiomers of ibuprofen and flurbiprofen were derivatized to yield the corresponding diastereomers. Chromatographic separation was achieved using a phenyl column with a run time of 20 min. (R)- and (S)-ibuprofen were quantitated at the multiple reaction monitoring (MRM) transition of m/z 360.2 ? 232.1, and (R)- and (S)-flurbiprofen were monitored at the MRM transition of m/z 398.3 ? 270.1. The method was validated for accuracy, precision, linearity, range, limit of quantitation (LOQ), limit of detection (LOD), selectivity, absolute recovery, matrix effect, dilution integrity, and evaluation of carry-over. Accuracy for (R)-ibuprofen ranged between –11.8% and 11.2%, and for (S)-ibuprofen between –8.6% and –0.3%. Precision for (R)-ibuprofen was ≤ 11.2%, and for (S)-ibuprofen ≤ 7.0%. The calibration curves were weighted (1/X2, n = 7) and were linear with r2 for (R)-ibuprofen ≥ 0.988 and for (S)-ibuprofen ≥ 0.990. The range of the method was 50 to 5000 ng/mL with the LOQ of 50 ng/mL, and LOD of 1 ng/mL, for (R)- and (S)-ibuprofen requiring 100 μL of sample. The method was applied successfully to a pharmacokinetic study with the administration of a single oral dose of ibuprofen capsules to human subjects.

A Study on the Degradation of Carbamazepine and Ibuprofen by TiO₂&ZnO Photocatalysis upon UV/Visible-Light Irradiation

The degradation of carbamazepine (CBZ) and ibuprofen (IBP) in aqueous matrices was investigated by TiO2 and ZnO photocatalysis initiated by UV-A and visible-light irradiation. Emphasis was given on the effect of operating parameters on the degradation effectiveness, such as catalyst type and loading (50 - 500 mg/L), initial drug concentration (10, 40, 80 mg/L) and wavelength of irradiation (200 - 600 nm). In an effort to understand the photocatalytic pathway for CBZ and IBP removal in terms of primary oxidants, the contribution of HO· was evaluated. With this scope, the radical-mediated process was suppressed by addition of an alcohol scavenger, isopropanol, (i-PrOH), described as the best free hydroxyl radical quencher. The photodegradation rate of the pharmaceuticals was monitored by high performance liquid chromatography (HPLC). According to the results, visible-light exposure, at λexc > 390 nm, takes place as a pure photocatalytic degradation reaction for both compounds. IBP was found to have overall high conversion rates, compared to CBZ. IBP oxidized fast under photocatalytic conditions, regardless the adverse effect of the increase of initial drug concentration, or low catalyst load, irradiation upon visible-light, by either titania or zinc oxide. Finally, addition of isopropanol showed a significant inhibition effect on the CBZ degradation, taken as an evidence of a solution-phase mechanism. In the case though of IBP degradation, the hole mechanism may be prevailing, suggested by the negligible effect upon addition of isopropanol indicating a direct electron transfer between holes (h+) and surface-bound IBP molecules. A plausible mechanism of IBP and CBZ photocatalysis was proposed and described.

Effect of Intravenous Ibuprofen on Ischemia-Reperfusion Injury Following Perioperative Tourniquet in Patients Undergoing Total Knee Arthroplasty

Oxidative stress occurs in the organism with ischemia due to tourniquet use and subsequent reperfusion. Oxidative stress increases postoperative morbidity. Some Non-Steroidal Anti-Inflammatory Drugs (NSAIDs) perform their anti-inflammatory effects in part by binding or inhibiting their formation of active oxygen radicals at the site of inflammation. In this study, we aimed to evaluate the effect of IV ibuprofen on ischemia-reperfusion injury (IRI) in patients undergoing total knee arthroplasty over oxidative stress parameters. The patients were randomly divided into two groups. Each patient’s protocol number, age, sex, body mass index (BMI), additional disease, drug use, tourniquet time, hemoglobin value, additional analgesic requirement and application, adverse reaction development on the first postoperative day were recorded in the research follow-up form. Both groups of patients;before anesthesia, 45 minutes after tourniquet application, 5 minutes after tourniquet lowering, 20 minutes after tourniquet lowering and at 24th-hour post-op;TOS, TAS, paraoxonase, arylesterase, myeloperoxidase, catalase, ceruloplasmin, albumin, IMA, thiol-disulfide balance tests were studied. Statistical analysis of test results was performed. We observed that antioxidants decreased and oxidants increased on the first postoperative day in both groups in patients who underwent total knee arthroplasty. The decrease in antioxidant parameters was higher in IV ibuprofen doses compared to the control group in the case group;these doses indicate that the drug adversely affects the organism in the fight against oxidative stress, which is an undesirable effect. To evaluate this negative effect of IV ibuprofen which is increasingly used in postoperative analgesia, studies with different doses of drugs and different surgeries may be needed.

Simultaneous colorimetric determination of morphine and ibuprofen based on the aggregation of gold nanoparticles using partial least square

In this work a new method is presented for simultaneous colorimetric determination of morphine （MOR） and ibuprofen （IBU） based on the aggregation of citrate-capped gold nanoparticles （AuNPs）. Citrate-capped AuNPs were aggregated in the presence of MOR and IBU. The difference in kinetics of AuNPs aggregation in the presence of MOR/IBU was used for simultaneous analysis of MOR and IBU. The formation and size of synthesized AuNPs and the aggregated forms were monitored by infra-red （IR） spectroscopy and transmission electron microscopy （TEM）, respectively. By adding MOR or IBU the absorbance was decreased at 520 nm and increased at 620 nm. The difference in kinetic profiles of aggregation was applied for simultaneous analysis of MOR and IBU using partial least square （PLS） regression as an efficient multivariate calibration method. The number of PLS latent variables was optimized by leave-one-out cross-validation method using predicted residual error sum of square. The proposed model exhibited a high capability in simultaneous prediction of MOR and IBU concentrations in real samples. The results showed linear ranges of 1.33-33.29 μg/mL （R2=0.9904） and 0.28-6.9 μg/mL （R2=0.9902） for MOR and IBU respectively with low detection limits of 0.15 and 0.03 μg/mL（S/N=5）.

Synthesis and Characterization of Ibuprofen-Rectorite Composites by Solution Intercalation Method

The ibuprofen-rectorite composites were prepared by the solution intercalation method using ibuprofen and rectorite as raw materials, and were characterized by X-ray diffraction （XRD） analysis, Fourier transform infrared analysis and scanning electron microscopy （SEM）. The experimental results show that the ibuprofen is intercalated into the interlayer spaces of rectorite. The values of the （001） peaks of the ibuprofen-rectorite composite are larger than that of Na-rectorite and reach the largest when the reaction time and ibuprofen amount is 2 h and 0.36 g, respectively. The layered structure of Na-rectorite is destroyed to some extent with the intercalation of ibuprofen into the interlayer space in the structure of Na-rectorite. A part of ibuprofen in the ibuprofen Na-rectorite covers on the surface of Na-rectorite besides some ibuprofen enters into the interlayer space.

Microwave-assisted Polymerization of ε-Caprolactone with Maleic Acid as Initiator and Drug Release Behavior of Ibuprofen-Poly(ε-caprolactone) System

Poly(e-caprolactone) (PCL) with weight-average molar mass over 10000 g/mol was synthesized by microwave-assisted ring-opening polymerization of e-caprolactone (e-CL) with maleic acid (MA) as initiator (2.45 GHz, 360 W, 85 min). Ibuprofen-PCL controlled release system was prepared directly by the ROP of e-CL in its mixture with ibuprofen. The release of ibuprofen from the system was sustained and steady.

Crystal Structure, Characterization and Enhanced Solubility of Ibuprofen by 2-Methylimidazolium Salt

Novel crystalline forms of ibuprofen(IBU) with 2-methylimidazole(2 MI) in a 1:1 molar ratio was synthesized by liquid-assisted grinding technique and characterized by single-crystal X-ray diffraction, infrared spectral(IR), powder X-ray diffraction(PXRD),differential scanning calormetry(DSC) and Hirshfeld surface analysis. The structure of IBU-2 MI salt is assembled via N(1)–H(1)+···O1 and N(2)–H(2)+···O(2) hydrogen bonds to form the zigzag-like 1 D chain structure. The original purpose was to solve the pH-dependent solubility defect of ibuprofen, and the result of pH dependent solubility experiments showed that the IBU-2 MI salt had a better solubility at the wide range of pH 4.00 to 9.18. Furthermore, the solubility of IBU-2 MI salt exhibits a dramatic increase(30-fold) in aqueous mediums.