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Dexibuprofen-loaded PEGylated PLGA nanospheres have been developed to improve the biopharmaceutical profile of the anti-inflammatory drug for ocular administration. Dexibuprofen is the active enantiomer of ibuprofen and therefore lower doses may be applied to achieve the same therapeutic level. According to this, two batches of nanospheres of different drug concentrations, 0.5 and 1.0 mg/ml respectively, have been developed (the latter corresponding to the therapeutic ibuprofen concentration for inflammatory eye diseases). Both batches were composed of negatively charged nanospheres (­−14.1 and ­−15.9 mV), with a mean particle size below 200 nm, and a high encapsulation efficiency (99%). X-ray, FTIR, and DSC analyses confirmed that the drug was dispersed inside the matrix of the nanospheres. While the in vitro release profile was sustained up to 12 h, the ex vivo corneal and scleral permeation profile demonstrated higher drug retention and permeation in the corneal tissue rather than in the sclera. These results were also confirmed by the quantification of dexibuprofen in ocular tissues after the in vivo administration of drug-loaded nanospheres. Cell viability studies confirmed that PEGylated-PLGA nanospheres were less cytotoxic than free dexibuprofen in the majority of the tested concentrations. Ocular in vitro (HET-CAM test) and in vivo (Draize test) tolerance assays demonstrated the non-irritant character of both nanosphere batches. In vivo anti-inflammatory effects were evaluated in albino rabbits before and after inflammation induction. Both batches confirmed to be effective to treat and prevent ocular inflammation. [ABSTRACT FROM AUTHOR]

Dexibuprofen (DXIBN) transdermal patches were formulated using various concentrations of selected polymeric excipients (matrix material; ethyl cellulose and polyvinylpyrrolidone, plasticizer (di-N-butyl phthalate), and a conventional permeation enhancer (almond oil)). Initial patch formulations were evaluated for their physiochemical properties (thickness, moisture uptake, final moisture content, and DXIBN content). Also, impact of patch components on resulting tensile strength andin vitropermeation were used to predict an optimal patch formulation using a quality-by-design (QbD) approach, which was subsequently evaluated and further compared with a commercial oral tablet dosage form forin vitroandin vivorelease (rabbit model). Initially formulated patches demonstrated uniform thickness (0.44 ± 0.02 cm), relatively low moisture uptake (7.87 ± 1.11 w/w %), and highly acceptable drug loading values (100.0 ± 0.026%). The tensile strength of patches increased significantly with matrix polymer concentration and to a lesser degree with increase in plasticizer and permeation enhancer content, although these affected the permeation of DXIBN. Predicted properties (tensile strength and DXIBN steady-state flux) for the QbD-optimized formulation were in close agreement to experimental results. The QbD optimal patch formulation behavior differed significantly from the commercial tablet formulationin vivo.Such model-based predictions (QbD approach) will reduce cost and time in formulation development sciences. [ABSTRACT FROM PUBLISHER]

[Display omitted] The purpose of the present study was to develop hydroxypropyl-β-cyclodextrin (HP-β-CD)-based solid dispersed granules as a superior system to solid dispersion. The solid dispersed granules and solid dispersion were compared in terms of powder property improvement, solubility increment and oral bioavailability enhancement of poorly water-soluble dexibuprofen. Solid dispersion (drug/HP-β-CD/Tween80 = 1:7:0.1, weight ratio) and solid dispersed granules (drug/HP-β-CD/Tween80/Microcrystalline cellulose = 1:7:0.1:4) were fabricated using a spray-dryer and fluid bed granulator, respectively. The HP-β-CD-based solid dispersed granules significantly improved solubility, dissolution profile and oral bioavailability of dexibuprofen compared to pure drug powder. Moreover, the solid dispersed granules maximised the oral bioavailability of dexibuprofen to the same extent as the solid dispersion. However, considerable improvements of powder and tablet properties were observed in solid dispersed granules as compared with solid dispersion. Therefore, HP-β-CD-based solid dispersed granules would be a prospective alternative to solid dispersion. [ABSTRACT FROM AUTHOR]

The aim of this research was to evaluate the gel properties, skin permeation and in vivo drug efficacy of a novel dexibuprofen-loaded emulsion gel for topical delivery. In this study, the dexibuprofen-loaded emulsion gel and ibuprofen-loaded emulsion gel were prepared with isopropanol, Tween 80, propylene glycol, isopropyl myristate and carbopol. Their mechanical properties such as hardness and adhesiveness were assessed. Moreover, their skin permeation, anti-inflammatory and anti-nociceptive efficacy were evaluated using Franz diffusion cell with the hairless mouse skin, the carrageenan-induced paw oedema test and paw pressure test in rat's hind paws compared with the commercial hydrogel, respectively. The dexibuprofen emulsion gel and ibuprofen emulsion gel provided significantly higher hardness and adhesiveness than the commercial hydrogel. The dexibuprofen emulsion gel enhanced skin permeability by about twofold and 3.5-fold without lag time compared to the ibuprofen emulsion gel and the commercial hydrogel, respectively, suggesting its faster skin permeation. Moreover, the anti-inflammatory efficacy and alleviation in carrageenan-induced inflammation was in the order of dexibuprofen emulsion gel > commercial hydrogel > ibuprofen emulsion gel. The dexibuprofen emulsion gel furnished significantly higher nociceptive thresholds than the ibuprofen emulsion gel and the commercial hydrogel, leading to the most improved anti-nociceptive efficacy. Thus, this dexibuprofen-loaded emulsion gel with good mechanical property, rapid skin permeation and excellent anti-inflammatory and anti-nociceptive efficacy would be a strong candidate for the topical delivery of anti-inflammatory dexibuprofen. [ABSTRACT FROM AUTHOR]

This pilot study aimed to explore the effectiveness and safety of dexibuprofen suppository in the treatment of PDA in preterm infants. Preterm infants with gestational age <34 weeks and color Doppler echocardiographic evidence of hemodynamically significant PDA (hs PDA) with systemic hypoperfusion was intended to be included into this study since January 2020. As of January 1, 2021, this trial had recruited 87 preterm infants who met the inclusion criteria. Neonates were admitted into hospital within 1 hour after birth and were randomly assigned into two groups. Group one included 44 preterm newborns administered with oral ibuprofen. Group two included 43 preterm newborns administered with dexibuprofen suppository. This preliminary study showed that rectal dexibuprofen and oral ibuprofen were both effective for the closure of PDA, and the closure rate of dexibuprofen suppository was comparable to that of oral ibuprofen after the 1st and 2nd courses of treatment. In addition, rectal dexibuprofen did not increase the incidence of adverse outcomes, including bronchopulmonary dysplasia, intraventricular hemorrhage, sepsis, and necrotising enterocolitis. This pilot study showed dexibuprofen suppository is as effective and safe as oral ibuprofen; yet, better designed, muticenter controlled studies are still needed.

This work aimed to incorporate Dexibuprofen (DXI), the pharmacologically active and more potent form of ibuprofen, into polymeric micelles based tablets with enhanced oral bioavailability. Thin film hydration technique was employed to prepare DXI polymeric micelles using Pluronic® F127 and/or P123 solutions in different ratios (ranging from 1:1 up to 1:10). Prepared micelles were characterized regarding particle size, drug loading and entrapment efficiency. Selected formulae were lyophilized in presence of cryoprotectants and subjected to solid-state characterization as well as scanning and transmission electron microscopy. Subsequently, tablets were prepared and evaluated in-vitro regarding physical properties and drug release. An in-vivo pharmacokinetic study was performed in six healthy human volunteers in comparison to the commercially available tablet of DXI. Solid-state characterization proved that DXI was homogenously dispersed in Pluronic micelles' matrices. Formula TF5 tablets comprising lyophilized micelles (F5; DXI: Pluronic F127 in 1:1 ratio and 0.25% mannitol) showed higher Cmax and earlier tmax values than those of the commercial formula, where the relative bioavailability was calculated to be 160.15%. The experimental evidence in this research leads to the conclusion that polymeric micelles present enabling properties for oral delivery of drugs with low solubility. [ABSTRACT FROM AUTHOR]

Dexibuprofen, is a practically water-insoluble nonsterodial anti-inflammatory drug which has a better anti-inflammatory effect than ibuprofen. A mixed hydrotropic solubilization technique was applied in order to improve the aqueous solubility and dissolution rate of dexibuprofen. Nine formulae were prepared using different concentrations of hydrotropic agents (sodium citrate dihydrate and urea). The prepared formulae were inspected visually for color and odor. Hygroscopicity, micromeretic properties, solubility, and pH for 1% aqueous solutions were determined. In-vitro dissolution studies of the different prepared formulae were performed adopting the USP XXII dissolution method type I basket apparatus method. The prepared formulae were characterized by infrared (IR) spectroscopy and differential scanning calorimetry (DSC). The prepared formulae were a white color, odorless, slightly hygroscopic and exhibited good flow properties. Formulae containing higher amounts of hydrotropic agents exhibited an increase in the pH, solubility, rate and amount of dexibuprofen released from the dissolution medium. The highest dissolution rate was achieved from the F9 formula at drug:sodium citrate dihydrate:urea ratio (1:3:7.5). IR and DSC thermograph of dexibuprofen, hydrotropic agents and prepared formulae indicated the presence of intermolecular interaction between drug and hydrotropic agents which increased solubility and dissolution rate of drug, also, there is no chemical interaction confirming the stability of the drug with hydrotropic agents. [ABSTRACT FROM AUTHOR]

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Background The aim of this study was to investigate the safety and efficacy of dexibuprofen compared to ibuprofen. Methods This double-blind, double-dummy study enrolled patients from January 2008 to May 2009 presenting at one of five tertiary care centers in Seoul, Korea with febrile illness who were then given one of three active treatments: one dose of dexibuprofen 2.5 or 5 mg/kg ( DEX 1); dexibuprofen 3.5 or 7 mg/kg ( DEX 2); or ibuprofen 5 or 10 mg/kg (control) syrup. Those with a temperature <38.5° C were given the lower dose. Temperature was measured every hour for 4 h. Primary study outcome was mean change in temperature 4 h after one dose. Results A total of 264 children (aged 6 months-14 years) with febrile illness due to upper respiratory tract infection were consecutively sampled and screened, with 260 randomized. No patients withdrew due to adverse effects. Mean temperature change after 4 h (mean ± SD: DEX 1, 0.99 ± 0.84°C; DEX 2, 1.12 ± 0.92°C; control, 1.38 ± 0.84°C) differed only between DEX 1 and controls ( P = 0.007, 95% confidence interval [CI]: −0.61 to −0.15). When groups were subdivided according to initial temperature, there were no significant differences in mean temperature change after 4 h between DEX 2 subgroups (<38.5° C, 0.88 ± 0.86°C; ≥38.5° C, 1.46 ± 0.90°C) and controls (1.07 ± 0.84°C and 1.72 ± 0.91°C, respectively), but there was a significant difference between DEX 1 (≥38.5° C, 1.25 ± 0.76°C) and controls ( P = 0.0222, 95% CI: −0.80 to −0.13). There were no significant differences in adverse events among groups. Conclusion Dexibuprofen (3.5 or 7 mg/kg) is as effective and tolerable as ibuprofen for fever caused by upper respiratory tract infection in children. [ABSTRACT FROM AUTHOR]

Objective: To develop a simple and sensitive method of ketorolac in drug free human plasma using high-performance liquid chromatographic (HPLC). Method: Ketorolac from blank plasma was extracted using protein precipitation method. Trichloro acetic acid (10%) was used as a protein precipitating agent and the percentage of recovery was calculated by adding known volume of dexibuprofen as internal standard. The HPLC separation was achieved on reversed-phase C18 column and the separations were detection by Photodiode Array (PDA) detector at 306 nm. Acetonitrile and 5 mM ammonium acetate (pH 3.5), in the ratio of 60:40% v/v was used as mobile phase at the isocratic flow rate of 1.0 ml/min. The method was validated according to FDA Guidance for Industry. Result: The percentage of recovery of ketorolac was 93.7 ± 0.12 (mean ± SD; n = 5). The linearity was achieved in this method range of 10.0e125.0 ng/ml with regression coefficient range of 0.999. Conclusion: Ketorolac bioanalytical method was developed and validated according to FDA Guidance for Industry. [ABSTRACT FROM AUTHOR]

We conducted an 8-week, open, randomized controlled clinical trial on 141 subjects affected by neuropathic pain to investigate the role of an adjunctive therapy added to the administration of dexibuprofen (400 mg twice a day) and based on a multi-ingredient formula (Lipicur), consisting of lipoic acid plus curcumin phytosome and piperine, in patients with a diagnosis of lumbar sciatica, lumbar disk herniation, and/or lumbar canal stenosis (96 subjects), or with carpal tunnel syndrome (45 subjects). A total of 135 participants completed the study. Treatment with the multi-ingredient formula (Lipicur) reduced neuropathic pain by more than 66% in both conditions (subjects with lumbar sciatica and with carpal tunnel syndrome), and these reductions were statistically significant. Moreover, the treatment reduced dexibuprofen use by about 40%. An add-on therapy with only lipoic acid has not shown any significant results. On the basis of its safety and efficacy, Lipicur could be considered an effective complementary therapy to be added to conventional treatments to achieve better efficacy in reducing neuropathic pain. [ABSTRACT FROM AUTHOR]

Ten prodrugs of dexibuprofen having ester and amide moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid chloride was condensed with different amino acid methyl ester hydrochlorides and five alcohols to afford the amide and ester prodrugs. All of the synthesized prodrugs were characterized by their mp, R, elemental analysis, FTIR, H NMR, and C NMR spectroscopy. The in vitro hydrolysis studies in plasma reflect prodrugs have been varied in terms of reactivity toward hydrolysis, owing to the different chemical structures. In alkyl substitution the branched chain alkyl substituents or aromatic substituents resulted in enhanced lipophilicity but diminished dissolution and hydrolysis rate. The amide prodrugs with branched and aromatic substitution can also be considered for sustained release. Prodrugs are less irritating to gastric mucosa than dexibuprofen. [ABSTRACT FROM AUTHOR]

A simple, rapid, and sensitive HPLC with UV detection was developed and validated for the determination of dexibuprofen in human plasma. The method involves extracting dexibuprofen with acetonitrile. Chromatographic separation was carried out on a C18 column using mixture of acetonitrile:methanol:potassium dihydrogen phosphate as mobile phase with UV detection at 222 nm. The retention time of dexibuprofen was 4.720 ± 0.3 min. The method was validated for selectivity, linearity, and range; intra-day and inter-day accuracy; and precision and stability. The developed and validated method was applied to a single oral dose of 400 mg dexibuprofen reference formulations (IBUSOFT 400 tablets manufactured by Emcure Pharmaceuticals Ltd, Pune, India) or test formulations (Medley Pharmaceuticals Ltd, Mumbai, India) that were administered to Indian healthy human male subjects. Serial blood samples were collected for 12 hr after administration of formulations. Pharmacokinetic parameters were determined for both the formulations. Cmax, AUC0-t and AUC0-inf, were evaluated for bioequivalence after log-transformation of data using ANOVA with a 90% confidence interval level. All of the tested parameters were within the acceptable range of 80–125%. The present method is simple and readily applicable to pharmacokinetic and routine bioequivalence studies of these compounds with an acceptable sensitivity. [ABSTRACT FROM AUTHOR]

Abstract: The solubilities of dexibuprofen in five solvents including methanol, n-butyl alcohol, isobutyl alcohol, n-amyl alcohol, and n-octyl alcohol were measured in the temperature range 263.15–293.15K under atmospheric pressure. The results indicate that the solubilities of dexibuprofen in the selected solvents increase with temperature. The experimental data were correlated by the modified Apelblat model which fit well with the experimental data. The dissolution enthalpy and entropy of both rac-ibuprofen and dexibuprofen were predicted. Moreover, the solubility data of both of them were correlated using two local composition models: NRTL 1 and UNIQUAC. It is indicated that for dexibuprofen, the NRTL 1 model can provide more accurate estimations of the solubility in the solvents of methanol, ethanol and n-propyl alcohol, while both NRTL 1 and UNIQUAC models can provide good estimations of the solubility in other solvents. For the rac-ibuprofen, the UNIQUAC model performs better to estimate the solubility in all the solvents. [Copyright &y& Elsevier]

The present investigation deals with the synthesis of novel prodrugs of dexibuprofen with amino acids with an aim to achieve potent anti-inflammatory activity and less gastrointestinal toxicity. Structures of synthesized compounds were confirmed by spectral and elemental analyses. In vitro hydrolytic studies in simulated intestinal fluid, 80% plasma and rat faecal matter showed satisfactory release of dexibuprofen due to enzymatic cleavage. The synthesized prodrugs were evaluated for anti-inflammatory activity, analgesia, ulcerogenicity and histopathology. The anti-inflammatory activity of dexibuprofen was 43.3% whereas an improved value of 73.4, 77.3, 72.8 and 64.5% was observed for the synthesized prodrugs. The percentage analgesia of the prodrugs increased, whereas a decrease in the mean ulcer index values than dexibuprofen was observed. The histopathological studies revealed less ulceration in the gastric region when treated with prodrugs. Thus, the prodrugs were proved to be better in action as compared with the parent drug. [ABSTRACT FROM AUTHOR]

Abstract: Background: Dexibuprofen is a pure S(+)-enantiomer product of racemic ibuprofen. A new extended-release form of dexibuprofen has recently been developed. Objective: We aimed to compare pharmacokinetic characteristics of controlled-release (CR) and immediate-release (IR) formulations of dexibuprofen after single and multiple oral doses in fasting healthy male Korean volunteers. Methods: Both single- and multiple-dose studies used an open-label, randomized, 2-way, crossover design. In the single-dose study, 24 subjects were administered a 600-mg CR or 300-mg IR formulation. In the multiple-dose study, 24 subjects were administered a 600-mg CR formulation q12h or 300-mg IR formulation q6h. Pharmacokinetic parameters of dexibuprofen were determined by noncompartmental analysis. Results: All formulations used in the single- and multiple-dose studies were well tolerated, and there were no severe adverse events. In the single-dose study, the mean (SD) AUC0–t was 155.60 (40.94) μg/h/mL for the CR formulation and 161.11 (37.50) μg/h/mL for the IR formulation; the mean (SD) Cmax values were 22.71 (6.64) and 23.77 (4.91) μg/mL, respectively; and the median Tmax values were 2.01 hours and 2.00 hours, respectively. The geometric mean ratios (90% CI) of the CR to IR formulations were 0.96 (0.92–1.00) for AUC0–t and 1.00 (0.87–1.14) for Cmax. In the multiple-dose study, the mean (SD) AUC0–τ values for CR and IR were 129.70 (23.72) μg/h/mL and 150.04 (27.09) μg/h/mL, respectively; the mean (SD) Cmax,ss values were 24.51 (5.12) and 21.69 (5.21) μg/mL, respectively; and the median Tmax.ss values were 2.51 hours and 5.25 hours, respectively. The geometric mean ratios (90% CI) of the CR to IR formulations were 0.86 (0.81–0.91) for AUC0–τ and 1.13 (1.03–1.24) for Cmax. Conclusions: The pharmacokinetic parameters of single and multiple administrations of dexibuprofen did not differ for the IR and CR formulations in this small, selected group of healthy male Korean subjects. Both formulations were well tolerated. [Copyright &y& Elsevier]

Abstract: The objective of this study was to achieve an optimal formulation of dexibuprofen dry elixir (DDE) for the improvement of dissolution rate and bioavailability. To control the release rate of dexibuprofen, Eudragit® RS was employed on the surface of DDE resulting in coated dexibuprofen dry elixir (CDDE). Physicochemical properties of DDE and CDDE such as particle size, SEM, DSC, and contents of dexibuprofen and ethanol were characterized. Pharmacokinetic parameters of dexibuprofen were evaluated in the rats after oral administration. The DDE and CDDE were spherical particles of 12 and 19μm, respectively. The dexibuprofen and ethanol contents in the DDE were dependent on the amount of dextrin and maintained for 90 days. The dissolution rate and bioavailability of dexibuprofen loaded in dry elixir were increased compared with those of dexibuprofen powder. Moreover, coating DDE with Eudragit® RS retarded the dissolution rate of dexibuprofen from DDE without reducing the bioavailability. Our results suggest that CDDE may be potential oral dosage forms to control the release and to improve the bioavailability of poorly water-soluble dexibuprofen. [Copyright &y& Elsevier]

Abstract: Animal models are used to research the mechanisms of pain and to mimic human pain. The purpose of this study was to determine the degree of interaction between dexketoprofen and dexibuprofen, by isobolographic analysis using the formalin orofacial assay in mice. This assay presents two-phase time course: an early short-lasting, phase I, starting immediately after the formalin injection producing a tonic acute pain, leaving a 15min quiescent period, followed by a prolonged, phase II, after the formalin and representing inflammatory pain. Administration of dexketoprofen or dexibuprofen produced a dose-dependent antinociception, with different potency, either during phases I or II. The co-administration of dexketoprofen and dexibuprofen produced synergism in phase I and II. In conclusion, both dexketoprofen and dexibuprofen are able to induce antinociception in the orofacial formalin assay. Their co-administration produced a synergism, which could be related to the different degree of COX inhibition and other mechanisms of analgesics. [ABSTRACT FROM AUTHOR]

The Cochrane Library of Systematic Reviews is published quarterly. Issue 3 2009 contains 3916 complete reviews, 1905 protocols for reviews in production, and 10,894 one-page summaries of systematic reviews published in the general medical literature. In addition, there are citations of 587,000 randomized controlled trials, and 11,800 cited papers in the Cochrane methodology register. The health technology assessment database contains 7947 citations. This edition of the Library contains 90 new reviews, of which 11 have potential relevance for practitioners in pain and palliative medicine. [ABSTRACT FROM AUTHOR]

The objective of this study was to improve the dissolution and solubility of dexibuprofen (DEX) using hydroxypropyl beta cyclodextrin (HPβCD) inclusion complexes and also to evaluate the effect of presence of hydrophilic polymers on solubilization efficiency of HPβCD. Three different methods (physical trituration, kneading and solvent evaporation) were used to prepare binary inclusion complexes at various drug-to-cyclodextrin weight ratios. An increase in solubility and drug release was observed with the kneading (KN) method at a DEX/HPβCD (1:4) weight ratio. The addition of hydrophilic polymers poloxamer-188 (PXM-188) and poloxamer-407 (PXM-407) at 2.5, 5.0, 10.0 and 20% w/w enhanced the complexation efficiency and solubility of DEX/HPβCD significantly. Fourier-transform infrared (FTIR) analysis revealed that DEX was successfully incorporated into the cyclodextrin cavity. Differential scanning calorimetry (DSC) and X-ray diffractometry (XRD) revealed less crystallinity of the drug and its entrapment in the cyclodextrin molecular cage. The addition of PXM-188 or PXM-407 reduced the strength of the DEX endothermic peak. With the addition of hydrophilic polymers, sharp and intense peaks of DEX disappeared. Finally, it was concluded that PXM-188 at a weight ratio of 10.0% w/w was the best candidate for improving solubility, stability and release rate of DEX. [ABSTRACT FROM AUTHOR]

Background: Primary dysmenorrhea is estimated to affect 40–50% of menstruating young women. Methods: Randomized, double-blind, 3-cycle crossover, active-controlled clinical trial conducted in 102 outpatients. Results: 102 patients entered the study and 77 were eligible for analyses. The mean (SD) age was 31.1 (7.0) years, and the mean cycle duration was 28.1 days (1.89) with a mean menstrual phase of 5.3 days (1.28). 40.26% of patients reported moderate pain from dysmenorrhea, and the remaining 59.74% reported severe pain. Compared to ibuprofen 400 mg, both dexibuprofen doses (200 and 300 mg) showed a trend towards superiority for sum of pain intensity difference (sum of PID), PID and total pain relief. Furthermore, dexibuprofen 200 mg had a faster onset of action compared to the double dose of ibuprofen (p = 0.035). A dose-effect relationship could be demonstrated for dexibuprofen in this visceral pain model. Tolerability was similar across all treatments. Conclusions: In patients experiencing acute visceral pain as a result of primary dysmenorrhea, dexibuprofen was associated with a dose-dependent effective analgesia; this effect was at least equivalent to that of the double dose of ibuprofen. With its lower body-loading dose, dexibuprofen expands the alternatives available to treat this condition. Copyright © 2008 S. Karger AG, Basel [ABSTRACT FROM AUTHOR]

WHAT IS ALREADY KNOWN ABOUT THIS SUBJECT • The analgesic and anti-inflammatory efficacy of dexibuprofen compared with ibuprofen in adults with osteoarthritis, rheumatoid arthritis and dental pain. WHAT THIS STUDY ADDS • Dexibuprofen is as effective and tolerable as ibuprofen, and a dose of 5 mg kg−1 of dexibuprofen would be sufficient to control fever caused by upper respiratory tract infection in children. AIM To evaluate the antipyretic efficacy and tolerability of dexibuprofen compared with ibuprofen in children with fever caused by upper respiratory tract infection (URTI). METHODS The study population consisted of children aged 6 months to 14 years. At the time of visit to the hospital, the children had fever; the cause of fever was determined to be URTI by a paediatrician based on history taking and physical examination. The study was a multicentre, randomized, double-blind, controlled parallel group, comparative, Phase 3 clinical trial, conducted at three hospitals. By using a computer-based random assignment program, the subjects were allocated to the following three groups: 5 mg kg−1 dexibuprofen group, 7 mg kg−1 dexibuprofen group, and 10 mg kg−1 ibuprofen group. RESULTS In the clinical trial of the antipyretic action of dexibuprofen in patients with fever caused by URTI, there was no statistically significant difference in maximal decrease of temperature and mean time to become apyrexial among the 5 mg kg−1 dexibuprofen, 7 mg kg−1 dexibuprofen and 10 mg kg−1 ibuprofen groups ( P > 0.05). There also was no significant difference in adverse drug reaction ( P > 0.05). CONCLUSIONS Dexibuprofen is as effective and tolerable as ibuprofen. A dose of 5 mg kg−1 and 7 mg kg−1 dexibuprofen in place of 10 mg kg−1 ibuprofen would be sufficient to control fever caused by URTI in children. [ABSTRACT FROM AUTHOR]

Dexibuprofen, or S(+)-ibuprofen, is the pharmacologically effective enantiomer of racemic ibuprofen. Since dexibuprofen has a low melting point, the amorphous form having a high melting point was prepared with the fused solid dispersion method. With the fused solid dispersion of dexibuprofen, immediate release tablets, extended release tablets, and dual release tablets were compressed and their dissolution profiles compared. The dissolution profiles of the extended release and the dual release tablet depended on the amount of used release modulators (PEO 5,000,000). The release profiles of extended release tablets and extended release part of dual release tablets were well fitted to zero-order release model. The correlation coefficient ranged from 0.982 to 0.995. A pharmacokinetic evaluation where healthy volunteers took tablets of DRT-1 (300 mg) once and the reference drug, two tablets of conventional immediate release tablet (Daxfen, 300 mg), with a 6-h interval between them was studied. The 90% confidence interval for the ratio of the logarithmically transformed AUC (0–24 h), Cmax (0–6 h), and Cmax (6–24 h) values of the dual release tablet compared to those of the conventional immediate release tablet were calculated to be between 0.9176 and 1.0007, 0.9240 and 1.1968, and 0.8713 and 1.1414, respectively. When the immediate release tablet was taken two times with a six hour interval between doses it showed a bioequivalent effect to taking the dual release tablet once within 12 h. The Cmax was reached due to the rapid absorption of the immediate release portion of the dual release tablet and the AUC was maintained due to continuous absorption of the extended release portion. [ABSTRACT FROM AUTHOR]

Abstract: A series of novel dexibuprofen derivatives covalently linked via alkylene spacers of variable length to tetraacetylated riboflavin have been developed. The target compounds became accessible by reaction of the chloromethyl ester of dexibuprofen with tetraacetylriboflavin (compound 7) or by synthesis of the appropriate N3-(ω-iodoalkyl)-2′,3′,4′,5′-Tetraacetylriboflavin followed by treatment with dexibuprofen (derivatives 8–11), respectively. Biological screening revealed that the target compounds exhibit antiproliferative effects on MCF-7 breast cancer and HT-29 colon carcinoma cells with IC50 values in the range of 8–15μM. Enzymatic studies on human platelets indicated significant COX-1 inhibitory activities of the target compounds. [Copyright &y& Elsevier]

Ibuprofen arginate is a salt formulation of ibuprofen designed to reach target concentrations rapidly. The primary objective of this study was to compare the 12-h pharmacokinetic profile of S(+)-ibuprofen following administration of single doses of ibuprofen arginate (600 mg) and dexibuprofen (400 mg) in healthy volunteers. Twenty-four volunteers were recruited into an open-label, randomised, two-period, single-centre study with crossover design. Both treatments were well tolerated. Ibuprofen arginate and dexibuprofen showed similar bioavailability for S(+)-ibuprofen. Compared with dexibuprofen, ibuprofen arginate demonstrated a 45% higher maximum concentration (Cmax), and a time to peak concentration (Tmax) 2 h sooner. Ibuprofen arginate approaches maximum concentrations of S(+)-ibuprofen faster and higher than dexibuprofen. [ABSTRACT FROM AUTHOR]

Objective: To assess the effect of a 2-week treatment with dexibuprofen, in comparison with ibuprofen and diclofenac, on pepsinogen plasma concentrations and gastrointestinal mucosa, as well as the correlation of these changes with gastrointestinal mucosal injury. Methods: 60 patients with rheumatologic disease in chronic therapy with NSAID, were included. After a 7-day rtm-in period patients were randomly assigned to receive a 14-day treatment with dexibuprofen (Group A; Day 1–3 = 400 mg t.i.d; Day 4–14 = 400 mg b.i.d.), ibuprofen (Group B; Day 1–3 = 800 mg t.i.d; Day 4–14 = 800 mg b.i.d.) or diclofenac (Group C; Day 1–3 = 50 mg t.i.d; Day 4–14 = 50 mg b.i.d.). Upper gastrointestinal endoscopy (Day 15), capsule-endoscopy (Day 16, 7 patients of each group) and determination of pepsinogen plasma concentrations were performed (basal and Day 15). A semiquantitative scale was designed for the assessment of the gastrointestinal mucosa. Results: No differences in plasma pepsinogen were found between treatment groups or gastrointestinal injury grades or between basal and post-therapy determinations. Dexibuprofen showed gastroduodenal and mucosal injury in fewer patients (42.1%) than was the case with ibuprofen (5%; p = 0.003) and diclofenac (30%; p = N.S.). Dexibuprofen administration was also associated with more patients having no intestinal mucosal damage (42.86% vs. 28.7% in the diclofenac group and 14.29% in the ibuprofen group; p = 0.0175). The rate of clinical adverse events was similar in Groups A, B and C (28%, 38% and 34%). Conclusions: Dexibuprofen showed a lower rate of gastroduodenal and intestinal mucosal injury. This effect was not mediated by modifications of plasma pepsinogen levels. [ABSTRACT FROM AUTHOR]

Rosin M, Kähler ST, Hessler M, Schwahn Ch, Kuhr A, Kocher T. The effect of a dexibuprofen mouth rinse on experimental gingivitis in humans. J Clin Periodontol 2005; 32: 617–621. doi: 10.1111/j.1600-051X.2005.00721.x.© Blackwell Munksgaard, 2005.The pharmacodynamic properties of ibuprofen are related nearly exclusively to theS(+)enantiomer (dexibuprofen). This study investigated the effect of a 1.5% dexibuprofen mouth rinse in an experimentally induced gingivitis.The trial was a randomized, double-blinded, placebo-controlled, two-period and two-sequence parallel group cross-over study in 24 healthy volunteers aged 21–30 years (16 males, eight females). Customized guards were worn during tooth brushing to prevent any plaque removal from the experimental area (first and second pre-molars and molars in one upper quadrant). After 22 days of plaque accumulation, the mouth rinses (1.5% dexibuprofen and placebo) were administered under supervision three times daily (rinsing for 1 min. with 15 ml) for 8 days. The wash-out time between the two study periods was 14 days. Parameters evaluated at days 0, 7, 14, 22, and 30 were the Löe&Silness gingival index (GI) and the Quigley&Hein plaque index (QHI). Data were tested for treatment, period, and carry-over effects (parametric cross-over analysis).There was no statistically significant difference (p=0.240) in GI between placebo and dexibuprofen. However, the decrease in QHI was significantly greater (p=0.019) with dexibuprofen as compared with the placebo.In the present study, a 1.5% dexibuprofen mouth rinse had no effect on gingivitis whereas an anti-plaque effect was demonstrated. [ABSTRACT FROM AUTHOR]

Dexibuprofen is the single pharmacologically effective enantiomer of rac-ibuprofen. Racibuprofen and dexibuprofen differ in their physico-chemical properties, in terms of their pharmacological properties and their metabolic profiles. Several clinical trials and post-marketing surveillance studies were performed to broaden the findings on dexibuprofen. In the last 5 years 4836 patients have been exposed to dexibuprofen in clinical trials and PMS trials. Only in 3.7% of patients adverse drug reactions have been reported and 3 serious adverse drug reactions (0.06%) were observed. In the dose ratio of 1 : 0.5 (rac-ibuprofen vs. dexibuprofen) at least equivalent efficacy was proven in acute mild to severe somatic and visceral pain models. Dexibuprofen has proven at least comparable efficacy to diclofenac, naproxen and celecoxib and has shown a favourable tolerability. The results suggest that dexibuprofen processed in a special crystal form is a safe and effective treatment for different pain conditions. [ABSTRACT FROM AUTHOR]

The efficacy study was performed to prove the equivalent efficacy of dexibuprofen compared to the double dose of racemic ibuprofen and to show a clinical dose-response relationship of dexibuprofen. The 1-year tolerability study was carried out to investigate the tolerability of dexibuprofen. In the efficacy study 178 inpatients with osteoarthritis of the hip were assigned to 600 or 1200 mg of dexibuprofen or 2400 mg of racemic ibuprofen daily. The primary end-point was the improvement of the WOMAC OA index. A 1-year open tolerability study included 223 outpatients pooled from six studies. The main parameter was the incidence of clinical adverse events. In the efficacy study the evaluation of the improvement of the WOMAC OA index showed equivalence of dexibuprofen 400 mg t.i.d. compared to racemic ibuprofen 800 mg t.i.d., with dexibuprofen being borderline superior (P = 0.055). The comparison between the 400 mg t.i.d. and 200 mg t.i.d. doses confirmed a significant superior efficacy of dexibuprofen 400 mg (P = 0.023). In the tolerability study the overall incidence of clinical adverse events was 15.2% (GI tract 11.7%, CNS 1.3%, skin 1.3%, others 0.9%). The active enantiomer dexibuprofen proved to be an effective NSAID with a significant dose-response relationship. Compared to the double dose of racemic ibuprofen, dexibuprofen was at least equally efficient, with borderline superiority over dexibuprofen (P = 0.055). The tolerability study in 223 patients on dexibuprofen showed an incidence of clinical adverse events of 15.2% after 12 months. The results of the studies suggest that dexibuprofen is an effective NSAID with good tolerability. [ABSTRACT FROM AUTHOR]

Several clinical trials, post-marketing surveillance studies and a meta-analysis were performed to obtain information about dose finding, pharmacokinetics, special indications, tolerability and compliance. In eight clinical trials, according to GCP, 1463 patients were included. Six of the trials were double-blind studies against placebo, racemic ibuprofen and diclofenac; the pharmacokinetic study and a long-term safety study were open studies. A meta-analysis of five clinical trials compared tolerability and safety data between dexibuprofen and racemic ibuprofen. Three PMS studies collected data on 7133 outpatients. All clinical trials and PMS studies have been published. In the dosage ratio 0.5:1, dexibuprofen was found to be at least as efficacious as racemic ibuprofen; 75% of the maximum daily dose of dexibuprofen was equally efficacious as 100% of MDD of diclofenac; no influence was found of meals on bioavailability and a significant doseresponse relationship; there was clinical efficacy in rheumatoid arthritis, ankylosing spondylitis, osteoarthritis of the hip, osteoarthritis of the knee, lumbar vertebral syndrome, distortion of the ankle joint and dysmenorrhoea; there was good tolerability compared to other NSAIDs: racemic ibuprofen showed a 30% and diclofenac a 90 % higher incidence of adverse drug reactions; the longterm study stated a 15.2% adverse drug event incidence; the incidence of adverse drug reactions in the PMS studies was between 5.5% and 7.4%, and withdrawals were between 2.3% and 2.7%. In conclusion, dexibuprofen (Seractil®) has the stature of a modern NSAID, combining the high efficacy of diclofenac with the good tolerability of ibuprofen, and need not hide behind the new generation of COX-2 inhibitors. [ABSTRACT FROM AUTHOR]