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Dexibuprofen is the pharmacologically active enantiomer of ibuprofen. However, its application as an antipyretic in children with fever caused by upper respiratory tract infection (URTI) requires more evidence. This study aimed to compare the antipyretic effect between dexibuprofen and ibuprofen in children with fever caused by URTI. Totally, 281 subjects were randomly assigned to the dexibuprofen (N = 142) or ibuprofen (N = 139) group at a 1:1 ratio. The subjects in the dexibuprofen or ibuprofen group were administered dexibuprofen + ibuprofen mimetic solution or ibuprofen + dexibuprofen mimetic solution 1‐4 times per day. Dexibuprofen was considered at least as effective as ibuprofen if the lower limit of the 95% confidence interval (CI) for the mean difference in axillary temperature change at 4 hours was greater than −0.3°C. The axillary temperature change after 4 hours was 1.3°C in the dexibuprofen group and 1.4°C in the ibuprofen group. The difference in axillary temperature change at 4 hours was −0.10°C (95% CI, −0.27 to 0.09°C) between the 2 groups, and the lower limit of the 95% CI was greater than −0.3°C, suggesting a comparable antipyretic effect of dexibuprofen to ibuprofen. The axillary temperature change from baseline, rates of normal axillary temperature at 4 hours, time to normal axillary temperature, and disease‐related symptoms at 24 or 48 hours were not different between the dexibuprofen and ibuprofen groups (all P  > .05). The incidence of adverse events did not differ between the 2 groups (all P > .05). In conclusion, dexibuprofen has a comparable antipyretic effect and safety profile to ibuprofen in Chinese children with fever caused by URTI. [ABSTRACT FROM AUTHOR]

Objective: This study aimed to develop a stable and scalable enteric film-coated tablet for the gastric irritant dexibuprofen. Methods: Utilizing direct compression with super-disintegration (crospovidone), the optimal core batches were coated with Opadry white seal coat and enterically coated with Eudragit®L100 with pigment (Talc), demonstrating a 12% weight increase; release and integrity were assessed using specific pH buffers and SEM, with stability testing confirming a six-month shelf life at 40 °C and 75% RH. Results: The optimized formulation achieved 99.87% release in phosphate buffer within 60 min, maintained integrity for 120 min in acidic conditions, and exhibited superior bioavailability compared to Innovifen with relative bioavailability ≈of 121% and elevated Cmax (18.35 µg/ml compared to 11.1 µg/ml). Conclusion: These results highlight the potential of this formulation to enhance patient safety and efficacy through delayed enteric technology and fast intestinal release. [ABSTRACT FROM AUTHOR]

The objective of this study was to design and develop an Agarose-based polymeric nanogel network system for solubility enhancement of a lipophilic drug, Dexibuprofen. Polymeric nanogels were synthesized through free radical polymerization where Agarose was cross-linked with 2-Acrylamido-2-methylpropane sulfonic acid (AMPS) in the presence of ammonium persulfate (APS) as an initiator and N, N'-Methylenebisacrylamide (MBA) as crosslinking agent. The resulting polymeric nanogels underwent a comprehensive characterization process including Fourier transform infrared (FTIR), particle size analysis, scanning electron microscopy (SEM), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD), and swelling studies to confirm the preparation of a stable polymeric nanogel system. FTIR spectral findings revealed that Agarose was chemically cross-linked with AMPS and confirmed the successful insertion of AMPS chains on the Agarose backbone. Particle size analysis revealed a diameter of 168 nm with a zeta potential of −9.91 mV, providing assurance of a stable polymeric nanogel system. SEM images depicted a highly porous surface. DSC and TGA results showed a more thermally stable network system than individual ingredients. Swelling studies revealed an increased swelling ratio of polymeric nanogels at phosphate buffer of pH 6.8 than acidic buffer of pH 1.2. Dexibuprofen was efficiently loaded into a polymeric nanogel system with a high entrapment efficiency of up to 80%. The solubility of the drug was enhanced when introduced to a polymeric nanogel formulation when compared to pure drug. The system reproducibility was evaluated through in vitro drug release and kinetic modeling of drug release. Toxicity studies confirmed the formulation's effectiveness, showcasing the developed polymeric nanogels as a promising option for delivering lipophilic drugs, with outstanding physicochemical properties, improved solubility, and minimal oral toxicity. [ABSTRACT FROM AUTHOR]

Alteration of solid form via a multicomponent crystal formation can be a choice to improve the solubility of a poor solubility drug, such as dexibuprofen. The purpose of this research was to produce dexibuprofen-caffeine (DXI-CAF) multicomponent crystal and to evaluate its solubility and dissolution rate. Preliminary investigation to predict the multicomponent crystal formation was conducted by observing crystal morphology by polarization microscope and knowing phase solubility type of DXI in caffeine solution. Liquid-assisted grinding (LAG) method was used to produce DXI-CAF multicomponent crystal and ethanol was used to accelerate its formation. Powder X-ray diffractometer (PXRD) and differential scanning calorimeter (DSC) were utilized to analyze DXI-CAF multicomponent crystal formation. Evaluation of physicochemical properties was carried out by the solubility testing in water and pH 1.2, 4.5, and 6.8. The dissolution rate tests were also performed in the same pH. The DXI-CAF showed a different crystal morphology from pure DXI and CAF after crystallized in ethanol. Meanwhile, a BS type curve was obtained from the determination of phase solubility. The LAG product revealed a distinctive PXRD pattern and DSC thermogram that was different from pure DXI and CAF, thereby indicating DXI-CAF multicomponent crystal formation. The increase in solubility and dissolution rate was shown in the DXI-CAF multicomponent crystal in all pH. Succinctly, DXICAF multicomponent crystal can be prepared by the LAG method which shows the potential in enhancing solubility and dissolution rate of dexibuprofen. [ABSTRACT FROM AUTHOR]

Ibuprofen, a nonsteroidal anti‐inflammatory drug, is considered a safe and effective analgesic for treating different types of pain and joint disorders. Dexibuprofen, S‐(+)‐ibuprofen, is the single pharmacologically active enantiomer of ibuprofen. It is more potent than the racemic formulation of ibuprofen in terms of analgesic and anti‐inflammatory properties and causes less acute gastric damage. For the first time, in the present single‐dose, randomized, open‐label, 2‐period crossover study, the safety and pharmacokinetic (PK) characteristics of a single‐dose dexibuprofen injection (0.2 g) were evaluated in healthy Chinese subjects and compared with the PK characteristics of a 0.2‐g ibuprofen injection. Five consecutive men and women were randomly administered a single dose of the 0.2‐g ibuprofen or 0.2‐g dexibuprofen injection after fasting in every period during the 5‐day interval. Then, plasma samples were collected for liquid chromatography–tandem mass spectrometric analysis. WinNonlin software was used for calculating the PK parameters. The geometric mean ratios of the 0.2‐g dexibuprofen injection/ibuprofen injection for maximal plasma concentration, area under the plasma concentration–time curve (AUC) from time 0 to the last quantifiable time point, and AUC from time 0 to infinity were 184.6%, 136.9%, and 134.4%, respectively. The dexibuprofen plasma exposure of the 0.15‐g dexibuprofen injection was comparable to that of the 0.2‐g ibuprofen injection, calculated using AUC from time 0 to infinity. [ABSTRACT FROM AUTHOR]

The paucity of multi-component compounds containing the non-steroidal anti-inflammatory drug (NSAID) S-(+)-ibuprofen (S-IBU) in combination with other drugs prompted the present study, which describes 1:1 salts of this active pharmaceutical ingredient (API) with the two most widely used antifibrinolytic APIs, namely 6-aminohexanoic acid (aminocaproic acid, ACA) and tranexamic acid (TXA), which are zwitterions in the solid state. Since NSAIDs are known to cause adverse side effects such as gastrointestinal ulceration, the presence of ACA and TXA in the salts with S-(+)-ibuprofen might counter these effects via their ability to prevent excessive bleeding. The salts were prepared by both the liquid-assisted grinding method and co-precipitation and were characterized by X-ray powder diffraction and single-crystal X-ray diffraction, thermal analysis, Fourier transform infrared spectroscopy, and solubility measurements. The X-ray analyses revealed a high degree of isostructurality, both at the level of their respective asymmetric units and in their extended crystal structures, with charge-assisted hydrogen bonds of the type N-H+⋅⋅⋅O− and O-H+⋅⋅⋅O− featuring prominently. The thermal analysis indicated that both salts had significantly higher thermal stability than S-(+)-ibuprofen. Solubility measurements in a simulated biological medium showed insignificant changes in the solubility of S-(+)-ibuprofen when tested in the form of the salts (S-IBU)−(ACA)+ and (S-IBU)−(TXA)+. [ABSTRACT FROM AUTHOR]

The purpose of this study was to develop a method for simultaneously separating ibuprofen enantiomers using electrospray ionization (ESI) liquid chromatography with tandem mass spectrometry (LC–MS/MS). LC–MS/MS was operated with negative ionization and multiple reaction monitoring modes; transitions were monitored at m/z of 205.1 > 160.9 for ibuprofen enantiomers, 208.1 > 163.9 for (S)-(+)-ibuprofen-d3 [internal standard 1 (IS1)], and 253.1 > 208.9 for (S)-(+)-ketoprofen (IS2), respectively. In a one-step liquid–liquid extraction, 10 μL plasma was extracted with ethyl acetate:methyl tertiary-butyl ether of 7:3. Enantiomer chromatographic separation was carried out with an isocratic mobile phase consisting of 0.008% formic acid in water–methanol (v/v) at a flow rate of 0.4 mL/min on a CHIRALCEL® OJ-3R column (150 × 4.6 mm, 3 µm). This method was fully validated for each enantiomer and results were in compliance with the regulatory guidelines of the U.S. Food and Drug Administration and the Korea Ministry of Food and Drug Safety. The validated assay was executed for nonclinical pharmacokinetic studies after oral and intravenous administration of racemic ibuprofen and dexibuprofen in beagle dogs. [ABSTRACT FROM AUTHOR]

The current study was designed to formulate ternary solid dispersions (TSDs) of dexibuprofen (Dex) by solvent evaporation to augment the solubility and dissolution profile, in turn providing gastric protection and effective anti-inflammatory activity. Initially, nine formulations (S1 to S9) of binary solid dispersions (BSDs) were developed. Formulation S1 comprising a 1:1 weight ratio of Dex and Syloid 244FP® was chosen as the optimum BSD formulation due to its better solubility profile. Afterward, 20 TSD formulations were developed using the optimum BSD. The formulation containing Syloid 244FP® with 40% Gelucire 48/16® (S18) and Poloxamer 188® (S23) successfully enhanced the solubility by 28.23 and 38.02 times, respectively, in pH 6.8, while dissolution was increased by 1.99- and 2.01-fold during the first 5 min as compared to pure drug. The in vivo gastroprotective study in rats suggested that the average gastric lesion index was in the order of pure Dex (8.33 ± 2.02) > S1 (7 ± 1.32) > S18 (2.17 ± 1.61) > S23 (1.83 ± 1.04) > control (0). The in vivo anti-inflammatory study in rats revealed that the percentage inhibition of swelling was in the order of S23 (71.47 ± 2.16) > S18 (64.8 ± 3.79) > S1 (54.14 ± 6.78) > pure drug (18.43 ± 2.21) > control (1.18 ± 0.64) after 6 h. ELISA results further confirmed the anti-inflammatory potential of the developed formulation, where low levels of IL-6 and TNF alpha were reported for animals treated with S23. Therefore, S23 could be considered an effective formulation that not only enhanced the solubility and bioavailability but also reduced the gastric irritation of Dex. [ABSTRACT FROM AUTHOR]

The present study was designed to formulate a 5% topical gel formulation containing dexibuprofen. Herein, we reported the utilization of different gelling polymers including hydroxyl propyl methyl cellulose (HPMC), carboxy methyl cellulose (CMC), carbopol 940 and leutrol F127 at three concentration levels. Overall, twelve trials (TD1 to TD12) were prepared in four batches (DEX-I to DEX-IV), each having three trial dexibuprofen gel formulations. All formulations were evaluated for organoleptic properties, clarity, pH, consistency, viscosity and spreadability. Trials of DEX-I and DEX- III batches (containing HPMC and carbopol 940polymers respectively), were a lack in smoothness, clarity and viscosity. Contra wise, TD5, TD6 dexibuprofen gel formulations of batch DEX-II and TD10, TD11 and TD12 of DEX-IV having CMC and lutrol® F127 correspondingly were found to be viscous and free from grittiness and precipitation. In vitro drug kinetics revealed the Weibull kinetic model as the best (r2>0.999, AIC 31.427-37.381, MSC 2.259-3.421). Stability testing was performed on the selected formulations (TD5, TD6, TD10, TD11 and TD12) having acceptable physicochemical attributes. Only TD11 and TD12 were found to be stable at room temperature after three months. Based on the findings, it is concluded that lutrol® F127 based dexibuprofen gel formulations delivered excellent spreadability, better drug release, and satisfactory stability profile. [ABSTRACT FROM AUTHOR]

The paucity of multi-component compounds containing the non-steroidal anti-inflammatory drug (NSAID) S-(+)-ibuprofen (S-IBU) in combination with other drugs prompted the present study, which describes 1:1 salts of this active pharmaceutical ingredient (API) with the two most widely used antifibrinolytic APIs, namely 6-aminohexanoic acid (aminocaproic acid, ACA) and tranexamic acid (TXA), which are zwitterions in the solid state. Since NSAIDs are known to cause adverse side effects such as gastrointestinal ulceration, the presence of ACA and TXA in the salts with S-(+)-ibuprofen might counter these effects via their ability to prevent excessive bleeding. The salts were prepared by both the liquid-assisted grinding method and co-precipitation and were characterized by X-ray powder diffraction and single-crystal X-ray diffraction, thermal analysis, Fourier transform infrared spectroscopy, and solubility measurements. The X-ray analyses revealed a high degree of isostructurality, both at the level of their respective asymmetric units and in their extended crystal structures, with charge-assisted hydrogen bonds of the type N-H+⋅⋅⋅O− and O-H+⋅⋅⋅O− featuring prominently. The thermal analysis indicated that both salts had significantly higher thermal stability than S-(+)-ibuprofen. Solubility measurements in a simulated biological medium showed insignificant changes in the solubility of S-(+)-ibuprofen when tested in the form of the salts (S-IBU)−(ACA)+ and (S-IBU)−(TXA)+.

The aim of this work was to design innovative nanostructured lipid carriers (NLCs) for the delivery of dexibuprofen (DXI) as an antiproliferative therapy against tumoral processes, and overcome its side effects. DXI-NLC samples were prepared with beeswax, Miglyol 812 and Tween 80 using high-pressure homogenization. A two-level factorial design 24 was applied to optimize the formulation, and physicochemical properties such as particle size, zeta potential, polydispersity index and entrapment efficiency were measured. Optimized parameters of DXI-NLCs exhibited a mean particle size of 152.3 nm, a polydispersity index below 0.2, and high DXI entrapment efficiency (higher than 99%). Moreover, DXI-NLCs provided a prolonged drug release, slower than the free DXI. DXI-NLCs were stable for 2 months and their morphology revealed that they possess a spherical shape. In vitro cytotoxicity and anticancer potential studies were performed towards prostate (PC-3) and breast (MDA-MB-468) cancer cell lines. The highest activity of DXI-NLCs was observed towards breast cancer cells, which were effectively inhibited at 3.4 μM. Therefore, DXI-NLCs constitute a promising antiproliferative therapy that has proven to be especially effective against breast cancer. [ABSTRACT FROM AUTHOR]

Abstract Background Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg−1 d−1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. Results Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. Conclusions Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy.

Objective: To compare the efficacy of dexibuprofen and ibuprofen for management of fever in febrile children. Methodology: This randomized clinical trial was conducted at the Pediatric Department, Lady Reading Hospital, Peshawar-Pakistan from October 2019 to April 2020. A total 150 patients were randomly allocated into two arms (Group I; dexibuprofen and Group II; Ibuprofen) and were enrolled through non-probability consecutive sampling technique. Participants between the ages of 6 months and 12 years, with febrile illness were enrolled in this study. Data analysis was done using Stata version 14, independent samples t-test was applied to compare mean change in temperature between the groups at different stages. Results: The mean age of the participants in the study was 2.84±1.655 years. The number of males were 107(71.33%) and females were 43(28.67%). There was no statistical difference in axillary temperature of participants in both groups before the intake of analgesics (p=0.527). The mean temperature after 4 hour of using dexibuprofen (100.14± 1.27 0F) was lower than ibuprofen (101.29±1.23 0F) with statistically significant difference (p<0.001). Conclusion: Dexibuprofen and ibuprofen are both effective in control of febrile illness but mean reduction in temperature for dexibuprofen was statistically more significant than ibuprofen. [ABSTRACT FROM AUTHOR]

Background: Several studies stablished a relationship between metabolic disturbances and Alzheimer´s disease (AD) where inflammation plays a pivotal role. However, mechanisms involved still remain unclear. In the present study, we aimed to evaluate central and peripheral effects of dexibuprofen (DXI) in the progression of AD in APPswe/PS1dE9 (APP/PS1) female mice, a familial AD model, fed with high fat diet (HFD). Animals were fed either with conventional chow or with HFD, from their weaning until their sacrifice, at 6 months. Moreover, mice were divided into subgroups to which were administered drinking water or water supplemented with DXI (20 mg kg−1 d−1) for 3 months. Before sacrifice, body weight, intraperitoneal glucose and insulin tolerance test (IP-ITT) were performed to evaluate peripheral parameters and also behavioral tests to determine cognitive decline. Moreover, molecular studies such as Western blot and RT-PCR were carried out in liver to confirm metabolic effects and in hippocampus to analyze several pathways considered hallmarks in AD. Results: Our studies demonstrate that DXI improved metabolic alterations observed in transgenic animals fed with HFD in vivo, data in accordance with those obtained at molecular level. Moreover, an improvement of cognitive decline and neuroinflammation among other alterations associated with AD were observed such as beta-amyloid plaque accumulation and unfolded protein response. Conclusions: Collectively, evidence suggest that chronic administration of DXI prevents the progression of AD through the regulation of inflammation which contribute to improve hallmarks of this pathology. Thus, this compound could constitute a novel therapeutic approach in the treatment of AD in a combined therapy. [ABSTRACT FROM AUTHOR]

Chitosan a poly-(D) glucosamine is a polysaccharide made by treating shrimp and other crustacean shells with the alkali sodium hydroxide. It is a hydrophilic polymer that helps to retain the drug inside the solid lipid nanoparticles (SLN's) and prolongs the release of drug from the carrier system. The purpose of the study was to formulate Chitosan decorated SLN's for the topical delivery of dexibuprofen by hot pressure homogenization technique. Blank SLN's, drug loaded SLN's and Chitosan decorated SLN's were prepared. Particle size, zeta potential and PDI were determined. FTIR study was conducted to evaluate the compatibility of excipients with the active drug. Surface morphology of SLN's was determined by field emission scanning electron microscope. Drug content and entrapment efficiency of SLN's were determined using indirect method. In vitro release and ex vivo permeation study of SLN's were carried out using Franz diffusion cell. The droplet size fell into the nano range i.e. 132±7 to 424±2 nm which is effective for topical drug delivery system. The PDI of formulations range from 0.21 to 0.42 which depicts the homogeneity of all the SLN's formulations. Vibrational analysis indicates that there is no interaction between active drug and excipient used in the formulation. The surface morphology revealed the spherical shape of Chitosan decorated SLN's. The in vitro release of formulations showed 79.91±1.07 to 89.94±1.8 % drug release. The drug permeation study showed high permeation of drug into the skin. The percent drug permeation ranges from 64.15±0.93 to 71.80±0.88% indicating good permeation of drug across the skin. Overall, SLN's are an effective carrier for topical delivery of dexibuprofen and thus bypasses side effects associated with oral delivery. [ABSTRACT FROM AUTHOR]

Dexibuprofen (DEXI) belongs to BCS class II drug with poor aqueous solubility resulting in poor bioavailability. To enhance solubility and bioavailability of DEXI, DEXI-loaded solid dispersion (SD) was formulated. DEXI-SDs were prepared by melting method and solvent evaporation method. Amphipathic polymer poloxamer 407 (pol 407) was selected based on solubility and dissolution tests. The ratio of DEXI:pol 407 was optimized as 1:2. The physicochemical properties, dissolution, and oral bioavailability of SD3 and SD6 were evaluated to compare preparation methods. The dissolution rate of DEXI from SD formulations was higher at pH 6.8 and pH 7.2 than at pH 1.2. Following oral administration in rats, the Cmax and AUClast of SD3 and SD6 formulations were significantly higher compared with raw DEXI. In addition, the SD6 formulation showed increased Cmax and AUClast by 1.34- and 1.33-fold, compared with those of SD3 formulation, respectively. These results demonstrated that SD formulation has excellent potential as a formulation for poorly soluble drug DEXI. [ABSTRACT FROM AUTHOR]

Jahangir Khan,1–3 Sajid Bashir,1 Muhammad Asif Khan,4 Mohammad Amin Mohammad,3 Mohammad Isreb3 1Department of Pharmacy, Faculty of Pharmacy, University of Sargodha, Sargodha, Pakistan; 2Department of Pharmacy, University of Malakand, Dīr, Khyber Pakhtunkhwa, Pakistan; 3School of Pharmacy, Institute of Life Science Research, School of Pharmacy, University of Bradford, Bradford, UK; 4Department of Pharmacy, Sarhad University Peshawar, Peshawar, Pakistan Purpose: Dexibuprofen is an enantiomer of ibuprofen with low bioavailability which results from its hydrophobic nature. Nanosuspensions have developed a podium to solve the in vitro dissolution problem that frequently occurs in current research. Materials and methods: The drug and polymer solutions were mixed in a microchannel fluid reactor and the successive embryonic nanosuspension was decanted into a vial having the polymer solution. The impact of different process and formulation parameters including inlet angle, antisolvent and solvent flow rate(s), mixing time, drug concentration, polymer type and concentration was evaluated. Results and discussion: Stable dexibuprofen nanocrystals with a particle size of 45±3.0 nm and polydispersity index of 0.19±0.06 were obtained. Differential scanning calorimetry and powder X-ray diffraction confirmed the crystallinity. The key parameters observed were inlet angle 10°, antisolvent to solvent volume of 2.0/0.5 mL/min, 60 minutes mixing with 5 minutes sonication, Poloxamer-407 with a concentration of 0.5% w/v and drug concentration (5 mg/mm). The 60-day stability studies revealed that the nanocrystals were stable at 4°C and 25°C. The scanning electron microscopy and transmission electron microscopy images showed crystalline morphology with a homogeneous distribution. Conclusion: Stable dexibuprofen nanocrystals with retentive distinctive characteristics and having marked dissolution rate compared to raw and marketed formulations were efficiently fabricated. In future perspectives, these nanocrystals could be converted to solid dosage form and the process can be industrialized by chemical engineering approach. Keywords: nanocrystal, dexibuprofen, microchannel fluidic reactor, process and formulation parameters

Abstract Background We aimed to compare the antipyretic efficacy, safety, and tolerability between oral dexibuprofen and intravenous propacetamol in children with upper respiratory tract infection (URTI) presenting with fever. Methods Patients aging from 6 months to 14 years admitted for URTI with axillary body temperature ≥ 38.0 °C were enrolled and randomized into the study or control group. Patients in the study group were intravenously infused with propacetamol and subsequently oral placebo medication was administered. Patients in the control group were intravenously infused with 100 mL of 0.9% sodium chloride solution without propacetamol and then oral dexibuprofen was administered. We checked the body temperature of all patients at 0.5 h (hr), 1 h, 1.5 h, 2 h, 3 h, 4 h, and 6 h after oral placebo or dexibuprofen had been applied. Results A total of 263 patients (125 in the study group) were finally enrolled. The body temperatures of patients in the study group were significantly lower until 2 h after administration (37.73 ± 0.58 vs 38.36 ± 0.69 °C (p

Naseem Ullah,1 Shahzeb Khan,1 Shaimaa Ahmed,2 Thirumala Govender,2 Hani S Faidah,3 Marcel de Matas,4 Muhammad Shahid,5 Muhammad Usman Minhas,6 Muhammad Sohail,7 Muhammad Khurram8 1Department of Pharmacy, University of Malakand, Chakdara, Pakistan; 2Discipline of Pharmaceutical Sciences, School of Health Sciences, University of KwaZulu-Natal, Durban, South Africa; 3Department of Microbiology, Faculty of Medicine, Umm Al Qura University, Makkah, Kingdom of Saudi Arabia; 4SEDA Pharmaceutical Development Services, The BioHub at Alderley Park, Cheshire, UK; 5Department of Pharmacy, Sarhad University of Science and Information Technology, Peshawar, Pakistan; 6Faculty of Pharmacy and Alternative Medicine, The Islamia University of Bahawalpur, Punjab, Pakistan; 7Department of Pharmacy, COMSATS, Abbottabad, Pakistan; 8Department of Pharmacy, Shaheed Benazir Bhutto University, Sheringal, Pakistan Background: The aim of this study was to prepare and evaluate the impact of polymers on fabricating stable dexibuprofen (Dexi) nanocrystals with enhanced therapeutic potential, using a low energy, anti-solvent precipitation method coupled with molecular modelling approach. Methods: Dexi nanocrystals were prepared using antisolvent precipitation with syringe pump. Crystallinity of the processed Dexi particles was confirmed using differential scanning calorimetry and powdered X-ray diffraction and transmission electron microscopy. Dissolution of Dexi nanocrystals was compared with raw Dexi and marketed tablets. Molecular modelling study was coupled with experimental studies to rationalise the appropriate polymers for stable Dexi nanocrystals. Antinociceptive study was carried out using balb mice. Results: Combinations of hydroxypropyl methylcellulose (HPMC)–polyvinyl pyrrolidone (PVP) and HPMC–Eudragit (EUD) were shown to be very effective in producing stable Dexi nanocrystals with particle sizes of 85.0±2.5 nm and 90±3.0 nm, and polydispersity of 0.179±0.01, 0.182±0.02, respectively. The stability studies conducted for 90 days demonstrated that nanocrystals stored at 2°C–8°C and 25°C were more stable than those at 40°C. The maximum recovery of Dexi nanocrystals was observed from the formulations using the combination of HPMC–PVP and HPMC–EUD, which equated to 98% and 94% of the nominal active drug content respectively. The saturation solubility of the Dexi nanocrystals was substantially increased to 270.0±3.5 µg/mL compared to the raw Dexi in water (51.0±2.0 µg/mL) and stabilizer solution (92.0±3.0 µg/mL). Enhanced dissolution rate (P

The study aimed to synthesize dexibuprofen (DXIBN) solid dispersions (SDS)-loaded hydroxypropylmethylcellulose (HPMC) and co-acrylic acid (AA)-based oral hydrogels via a modest solvent evaporation technique. Free radical polymerization technique was used to prepare HPMC-co-AA hydrogels using EGDMA as cross-linker and ammonium per sulfate as initiator. SDS of DXIBN were prepared using Soluplus® (SLPS®) as a solubilizing agent. The solubility of pure DXIBN and the respective SDS was analyzed in phosphate buffer solutions (PBS) at varying pH (1.2, 6.8 and 7.4 pH) at temperatures (25 and 37 °C). The physiochemical characterizations: swelling analysis, diffusion co-efficient, porosity and sol-gel analysis, Fourier transform infrared spectroscopy (FTIR) and differential scanning calorimetry (DSC), swelling behavior and release studies (at pH 1.2 and 7.4) were steered. The solubility was found to be significantly (p <.05) improved up to twofolds as compared to pure DXIBN. The hydrogels with higher concentrations of HPMC and AA showed significant (p <.05) increase in swelling, whereas there was a significant (p <.05) decrease with higher concentration of cross-linker EGDMA. The release kinetics applied trailed overall the non-Fickian release mechanism. The existing work exhibited was found to be improved DXIBN solubility using Soluplus via SDS technique and a stable HPMC-co-AA DXIBN release retardant hydrogel as an exceptional safer tool for the treatment of rheumatoid arthritis. [ABSTRACT FROM AUTHOR]

Aim: In particular, the objective of this research work is related to treating patients in need of nonsteroidal anti-inflammatory therapy. The study was aimed to prepare topical administrations of dexibuprofen in the form of a transdermal gel so that the problems associated with oral administration of dexibuprofen are avoided. This present study is focused to study the stability profile for the prepared hydroalcoholic and hydrogels of dexibuprofen. Materials and Methods: The dexibuprofen hydroalcoholic and hydrogels were prepared by simple dispersion techniques. The prepared hydroalcoholic and hydrogels were subjected to stability under accelerated stability (40°C/75% RH) condition. The stability samples are withdrawn at predetermined time intervals, drug content and related substances were analyzed by the developed high-performance liquid chromatography technique. Results: There are observed highest unknown impurity in hydroalcoholic gel due to drug degradation. Hence, the optimized formulation G9 of hydroalcoholic gel was prepared with free from alcohol (hydrogel) to maintain the stability. The dexibuprofen hydrogel was not observed any significant unknown impurity; it can able to maintain the shelf life. Conclusion: Since an effort was made to formulate a stable transdermal gel, due to the related substances observed on the hydroalcoholic gel, alcohol free dexibuprofen hydrogel shows no change in the drug content and related substances. The results are encouraging the formulations of the hydrogel. [ABSTRACT FROM AUTHOR]

The aim of the present study is to elucidate the neuronal pathways associated to NSAIDs causing a reduction of the risk and progression of Alzheimer's disease. The research was developed administering the active enantiomer of ibuprofen, dexibuprofen (DXI), in order to reduce associated gastric toxicity. DXI was administered from three to six-month-old female APPswe/PS1dE9 mice as a model of familial Alzheimer's disease. DXI treatment reduced the activation of glial cells and the cytokine release involved in the neurodegenerative process, especially TNFα. Moreover, DXI reduced soluble β-amyloid (Aβ1-42) plaque deposition by decreasing APP, BACE1 and facilitating Aβ degradation by enhancing insulin-degrading enzyme. DXI also decreased TAU hyperphosphorylation inhibiting c-Abl/CABLES/p-CDK5 activation signal pathway and prevented spatial learning and memory impairment in transgenic mice. Therefore, chronic DXI treatment could constitute a potential AD-modifying drug, both restoring cognitive functions and reversing multiple brain neuropathological hallmarks.

In the present study, in order to improve the solubility and bioavailability of poorly water-soluble dexibuprofen, a novel dexibuprofen-loaded solid dispersion was developed using the spray-drying technique. The controlled-release dexibuprofen formulation was developed by combining the immediate-release dispersion powder and the sustained-release formula. The solid dispersion composed of dexibuprofen/poloxamer 407/hydroxypropyl methylcellulose (HPMC) 2910 (50 cps)/sodium lauryl sulfate (SLS) (10/1/4/0.1 mg) was selected as the immediate-release formulation due to its increased solubility and dissolution rate. This immediate-release formulation showed a significantly higher initial plasma concentration, AUC, and Cmax of dexibuprofen than those of dexibuprofen powder. Based on the prolonged effect of high plasma concentration, the formulation consisting of dexibuprofen/ethylcellulose/HPMC 2910 (4000 cps)/magnesium stearate (66/16.5/16.5/1 mg) was selected as the sustained-release formulation. Finally, the controlled-release (CR) formulation was prepared by encapsulating the immediate-release and sustained-release formulations in hard gelatin capsules. The proposed CR formulation showed enhanced AUC (5.5-fold) and Cmax (3.5-fold) compared to dexibuprofen powder. The results of the present study suggest that the CR formulation containing dexibuprofen may be a potential oral dosage form for a fast onset and a prolonged effect of poorly water-soluble dexibuprofen. [ABSTRACT FROM AUTHOR]

Emulgels have emerged as a promising drug delivery system for the delivery of hydrophobic drugs. The objective of the study was to prepare emulgel of Dexibuprofen, a NSAID, using Carbapol 940 as a gelling agent. Clove oil and Mentha oil were used as penetration enhancers. The emulsion was prepared and it was added in gel base. The formulations were evaluated for rheological studies, spreading coefficient studies, bioadhesion strength, skin irritation studies, in vitro release, ex vivo release studies, anti-inflammatory activity and analgesic activity. Formulation showed comparable analgesic and anti-inflammatory activity when they compared with marketed diclofenac sodium gel. So, it can be concluded that topical emulgel of Dexibuprofen possess an effective anti-inflammatory and analgesic activity. [ABSTRACT FROM AUTHOR]

S-(+) enantiomer of ibuprofen (IBU) dexibuprofen (DXI) is known to be more potent than its R-(−) form and exhibits many advantages over the racemic mixture of IBU such as lower toxicity, greater clinical efficacy, and lesser variability in therapeutic effects. Moreover, DXI potential has been recently advocated to reduce cancer development and prevent the development of neurodegenerative diseases in addition to its anti-inflammatory properties. During the last decade, many attempts have been made to design novel formulations of DXI aimed at increasing its therapeutic benefits and minimizing the adverse effects. Therefore, this article summarizes pharmacological information about DXI, its pharmacokinetics, safety, and therapeutic outcomes. Moreover, modified DXI drug delivery approaches are extensively discussed. Recent studies of DXI prodrugs and novel DXI nanoformulations are analyzed as well as reviewing their efficacy for ocular, skin, and oral applications.

Ocular inflammation is one of the most prevalent diseases in ophthalmology, which can affect various parts of the eye or the surrounding tissues. Non-steroidal anti-inflammatory drugs (NSAIDs) such as ibuprofen, are commonly used to treat ocular inflammation in the form of eye-drops. However, their bioavailability in ocular tissues is very low (less than 5%). Therefore, drug delivery systems such as biodegradable polymeric PLGA nanoparticles constitute a suitable alternative to topical eye administration, as they can improve ocular bioavailability and simultaneously reduce drug induced side effects. Moreover, their prolonged drug release can enhance patient treatment adherence as they require fewer administrations. Therefore, several formulations of PLGA based nanoparticles encapsulating dexibuprofen (active enantiomer of Ibuprofen) were prepared using the solvent displacement method employing different surfactants. The formulations have been characterized and their interactions with a customized lipid corneal membrane model were studied. Ex vivo permeation through ocular tissues and in vivo anti-inflammatory efficacy have also been studied.

ABSTRACT Interpolyelectrolyte complexes, which constitute a type of polymeric material obtained through the self-assembly of oppositely charged polymers, exhibit interesting properties for use in the design of smart matrices for drug delivery. In the present study, a stoichiometric interpolyelectrolyte complex (SIPEC) composed of Eudragit E® and Eudragit® L100 was obtained at pH 6.0 and characterized and evaluated as a hydrophilic matrix for dexibuprofen. The formation of a SIPEC was monitored by ζ-potential measurements and characterized using infrared spectroscopy, thermal analysis, and scanning electron microscopy. The results indicated that a SIPEC obtained under these conditions can be used as a matrix for controlling the release of dexibuprofen and exhibit a pH-triggered release.

Montmorillonite (Mt) plays a very important role in controlling drug delivery. In this paper, the hydrochloric acid (HCl) treated Mt. was exploited to obtain composites, which were able to enhance dexibuprofen (IBU) loading and achieve to sustain release drug. The textural properties of the Mt. were strongly dependent on the treatment of HCl. The drug loading of pristine Mt. was 190 mg/g, while it was increased to 298 mg/g for Acid-Mt. In vitro release showed that the IBU was released about 92% from IBU/Acid-Mt within 12 h, while the pure IBU was released all within 4 h in simulated intestinal fluid, which meant that the IBU/Acid-Mt were able to retard the drug release with a controlled manner. The release profiles of IBU from composites were fitted by Higuchi and Korsmeyer-Peppas equations, which manifested that diffusion sustained release dominated the main mechanism. Meanwhile, in vivo pharmacokinetics studies in rats displayed that the IBU/Acid-Mt exhibited better gradual drug release than the commercial IBU suspension. For the IBU/Acid-Mt composites, the area under the plasma concentration-time curve from 0 to 24 h ( AUC 0–24 ) and mean residence time ( MRT 0–24 ) were 644.49 ± 73.26 μg/h/mL and 7.65 ± 0.48 h, both of which were significantly larger than commercial IBU suspension ( AUC 0–24 of 439.88 ± 84.41 μg/h/mL and MRT 0–24 of 3.10 ± 0.38 h), respectively ( P  < 0.05). The relative bioavailability of IBU/Acid-Mt was 154.11% ± 27.41% compared to commercial IBU suspension. As a result, the IBU/Acid-Mt is expected to achieve sustained release and extend residence time in plasma. [ABSTRACT FROM AUTHOR]

Healthcare professionals including physicians and pharmacists have been trying since long to come across and work out regarding the issue of generic alternatives, which is highly affected by factors like therapeutic efficacy, cost effectiveness, aesthetic and elegant appearance and implementation of packaging number over the drug product. However, the community pharmacist professionals are also facing difficulty in making decision regarding selection and dispensing the most efficacious brand to the patients. In this regard, the initiation of recent approaches for the development of amenable drug products has led to evolve the concept of generating new avenues for achieving higher patient compliance. Hence, the objective of this study was to evaluate the quality attributes and make comparisons regarding different brands of Dexibuprofen available in market of Karachi, Pakistan. The study is based on evaluation of physical chemical parameters of five different brands. Moreover, a comparative dissolution profile of selected brands of Dexibuprofen was also performed by applying numerous approaches. DEX-1was selected as reference while DEX-2-DEX-5was selected as test brands. Results of all the selected brands met all the compendial requirements. Interpretation of the entire aforementioned test was evaluated using model independent, model- dependent and one – way ANOVA. The work presented in this study has been designed to provide quality standard products easily accessible in Pakistani market. [ABSTRACT FROM AUTHOR]

The main purpose of work was to formulate dexibuprofen loaded eudragit L-100 micro particles to acquire site specific delivery of dexibuprofen. Micro particles were formulated by an emulsion solvent evaporation method. Four formulations F1, F2, F3 and F4 having drug to polymer ratio 1:1, 1:2, 1:3 and 1:4, respectively were prepared and characterized. The rheological properties manifested that micro particles were worthy for further pharmaceutical exploitation. No notable drug polymer interaction was perceived in FT-IR spectroscopy. SEM micrographs showed rough surface of micro particles. The resulting micro particles had high entrapment efficiency greater than 70%. The in vitro dexibuprofen release at pH 1.2 exhibited poor drug release with less than 21% while at pH 6.8, 60% of the dexibuprofen was released up till 8th hour. The dexibuprofen release was modified by altering polymer concentration in the formulation. The subsequent micro particles were found to be best fit with zero-order release model. Micro particles were efficiently formulated with a focus to release the drug majorly in small intestine. With increase of polymer concentration enhanced entrapment efficiency and decelerated dexibuprofen release from the micro particles has been achieved. In vitro dexibuprofen studies verified the gastro-resistant property of micro particles thus qualify site specific release in gastrointestinal tract. [ABSTRACT FROM AUTHOR]

Objective: The aim of the present research was formulation and evaluation of anti-inflammatory drug dexibuprofen loaded chitosan-based polymeric nanoparticles (NPs) for the controlled release of dexibuprofen using different concentrations of chitosan and surfactant. Materials and Methods: Dexibuprofen, a nonsteroidal anti-inflammatory drug was encapsulated with the polymer by emulsion-droplet coalescence method (DNP1-DNP5). The NPs were characterized by drug content, particle size, zeta potential, encapsulation efficiency, and in vitro drug release. Result: DNP3 was selected as best formulation due to its ideal particle size (437.6 nm), high entrapment efficiency (88.54%), and desirable drug release (99.81 ± 0.92% at the end of 24 h). Conclusion: The present study can be concluded that the newly formulated controlled release nanoparticulate drug delivery system of dexibuprofen may be ideal and effective in the management of pain due to arthritis by allowing the drug to release continuously for 24 h. [ABSTRACT FROM AUTHOR]

Objective:This study was aimed to enhance aqueous solubility of dexibuprofen through designing β-cyclodextrin (βCD) hydrogel nanoparticles and to evaluate toxicological potential through acute toxicity studies in rats. Significance:Dexibuprofen is a non-steroidal analgesic and anti-inflammatory drug that is one of safest over the counter medications. However, its clinical effectiveness is hampered due to poor aqueous solubility. Methods:βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM andin-vitrodissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles. Results:βCD hydrogel nanoparticles dramatically enhanced the drug loading and solubilization efficiency of dexibuprofen in aqueous media. FTIR, TGA and DSC studies confirmed the formation of new and a stable nano-polymeric network and interactions of dexibuprofen with these nanoparticles. Resulting nanoparticles were highly porous with 287 nm in size. XRD analysis revealed pronounced reduction in crystalline nature of dexibuprofen within nanoparticles. Release of dexibuprofen in βCD hydrogel nanoparticles was significantly higher compared with dexibuprofen tablet at pH 1.2 and 6.8. In acute toxicity studies, no significant changes in behavioral, physiological, biochemical or histopathologic parameters of animals were observed. Conclusions:The efficient preparation, high solubility, excellent physicochemical characteristics, improved dissolution and non-toxic βCD hydrogel nanoparticles may be a promising approach for oral delivery of lipophilic drugs. [ABSTRACT FROM PUBLISHER]

Three amide derivatives – methyl-2-[2-(4-isobutylphenyl)propanamido]propanoate (Dex-2), methyl 2-[2-(4-isobutylphenyl) propanamido]-3-phenylpropanoate (Dex-3) and methyl 2-[2-(4-isobutylphenyl)-propanamido]-4-methylpentanoate (Dex-4) of dexibuprofen (Dex-1) 2-(4-isobutylphenyl)propanoic acid were synthesized and conformed for structures by physical data and spectral analysis. Further, all the compounds were studied for their binding with ds.DNA through experimental (UV-visible/and fluorescence spectroscopy, cyclic voltammetry) and theoretical (molecular docking) techniques. Spectral and voltammetric responses as well as kinetic and thermodynamic data interpretations at stomach (4.7) and blood (7.4) pH and at human body temperature (37 °C) indicated spontaneous interaction of all the compounds with DNA via intercalation and external bindings. The binding constants ( K b ) and Gibbs free energy changes (− Δ G ) were evaluated greater at pH 7.4 attributing comparatively more significant binding of all the compounds with DNA at blood pH. Among all compounds, Dex-4 showed greater binding with DNA at both pH with greater K b values i.e., {UV-visible: pH 4.7 (2.36 × 10 4 M − 1 ); pH 7.4 (2.42 × 10 4 M − 1 ), fluorescence: pH 4.7 (2.24 × 10 4 M − 1 ); pH 7.4 (2.56 × 10 4 M − 1 ) and CV: pH 4.7 (4.06 × 10 4 M − 1 ); pH 7.4 (4.89 × 10 4 M − 1 )}. Binding site size (n) at both pH values was evaluated n ≥ 1 for Dex-2 and Dex-4 which assured intercalation as a major mode of interaction between compounds and DNA. For Dex-1 and Dex-3 (n) was evaluated n ≤ 1 at both pH values and the values n < 1 indicated the possibility of binding via groove or electrostatic interactions. Electrochemical processes were found diffusion controlled and diffusion coefficients (D o ) for all the compounds – DNA adducts were evaluated lesser than unbound compounds. Docking studies further supported DNA binding evidences obtained from spectral and electrochemical investigations. [ABSTRACT FROM AUTHOR]

Dexibuprofen loaded pegylated poly(lactic-co-glycolic) nanospheres prepared by solvent diffusion method were designed to increase Dexibuprofen brain delivery reducing systemic side effects. Nanospheres exhibited a mean particle size around 200 nm (195.4 nm), monomodal population and negative surface charge. Drug loaded nanospheres showed a sustained release profile, allowing to modify the posology in vivo . Nanospheres were non-toxic neither in brain endothelial cells nor astrocytes and do not cause blood–brain barrier disruption. Nanospheres were able to partially cross the cells barrier and release the drug after co-culture in vitro experiments, increasing Dexibuprofen permeation coefficient. Behavioral tests performed in APPswe/PS1dE9 mice (mice model of familial Alzheimer's disease) showed that nanospheres reduce memory impairment more efficiently than the free drug. Developed nanospheres decrease brain inflammation leading to β-amyloid plaques reduction. According to these results, chronical oral Dexibuprofen pegylated poly(lactic-co-glycolic) nanosystems could constitute a suitable strategy for the prevention of neurodegeneration. [ABSTRACT FROM AUTHOR]

Prodrugs of dexibuprofen having ester moieties instead of free carboxylic acid which involves in gastrointestinal side effects have been synthesized. Dexibuprofen acid was condensed with different alcohols/phenols to afford the ester prodrugs. All of the synthesized prodrugs were characterized by their physical attributes, elemental analysis, FT-IR, 1 H-NMR, and 13 C-NMR spectroscopy. The in vitro anti-inflammatory studies was done by chemiluminescence technique reflect prodrugs have been more potent, owing to the different chemical structures. Lipoxygenase enzyme inhibition assay was also assess and found compound DR7 with IC 50 =19.8 μM), DR9 (IC 50 =24.8 μM) and DR3 (IC 50 =47.2 μM) as compared with Dexibuprofen (IC 50 =156.6 μM). It was also evaluated for docking studies revealed that DR7 has found to be more potent anti-inflammatory against 5-LOX (3 V99) as well as analgesic against COX-II (5KIR) enzyme. Anti-oxidant activities were also performed, DR3 (86.9 %), DR5 (83.5 %), DR7 (93.9 %) and DR9 (87.4 %) were found to be more anti-oxidant as compared to (2S)-2-[4-(2-methylpropyl)phenyl]propanoic acid (52.7 %)., (© 2023 Wiley-VHCA AG, Zurich, Switzerland.)

Dexibuprofen-antioxidant conjugates were synthesized with the aim to reduce its gastrointestinal effects. The esters analogs of dexibuprofen 5a-c were obtained by reacting its -COOH group with chloroacetyl derivatives 3a-c. The in vitro hydrolysis data confirmed that synthesized prodrugs 5a-c were stable in stomach while undergo significant hydrolysis in 80% human plasma and thus release free dexibuprofen. The minimum reversion was observed at pH 1.2 suggesting that prodrugs are less irritating to stomach than dexibuprofen. The anti-inflammatory activity of 5c (p < 0.001) is more significant than the parent dexibuprofen. The prodrug 5c produced maximum inhibition (42.06%) of paw-edema against egg-albumin induced inflammation in mice. Anti-pyretic effects in mice indicated that prodrugs 5a and 5b showed significant inhibition of pyrexia (p < 0.001). The analgesic activity of 5a is more pronounced compared to other synthesized prodrugs. The mean percent inhibition indicated that the prodrug 5a was more active in decreasing the number of writhes induced by acetic acid than standard dexibuprofen. The ulcerogenic activity results assured that synthesized prodrugs produce less gastrointestinal adverse effects than dexibuprofen. The ex vivo antiplatelet aggregation activity results also confirmed that synthesized prodrugs are less irritant to gastrointestinal mucosa than the parent dexibuprofen. Molecular docking analysis showed that the prodrugs 5a-c interacts with the residues present in active binding sites of target protein. The stability of drug-target complexes is verified by molecular dynamic simulation study. It exhibited that synthesized prodrugs formed stable complexes with the COX-2 protein thus support our wet lab results. It is therefore concluded that the synthesized prodrugs have promising pharmacological activities with reduced gastrointestinal adverse effects than the parent drug. [ABSTRACT FROM AUTHOR]