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Ocular inflammation is one of the most prevalent diseases in ophthalmology and it is currently treated using eye drops of nonsteroidal antiinflammatory drugs such as dexibuprofen (DXI). However, their bioavailability is low and therefore, PLGA nanoparticles constitute a suitable approach to be administered as eyedrops. Therefore, DXI has been encapsulated into PLGA nanoparticles (DXI-NPs). Although the eye, and specifically the cornea, suffers from age-related changes in its composition, current medications are not focused on these variations. Therefore, to elucidate the interaction mechanism of DXI-NPs with the cornea in relation with age, two different corneal membrane models have been developed (corresponding to adult and elder population) using lipid monolayers, large and giant unilamellar vesicles. Interactions of both DXI and DXI-NPs were studied with these models by means of Langmuir balance technique, dipole potential, anisotropy and confocal microscopy. In addition, fluorescently labelled nanoparticles were administered to mice in order to corroborate these data obtained in vitro. It was observed that DXI-NPs interact with lipid membranes through an adhesion process, mainly in the rigid regions and afterwards DXI-NPs are internalized by a wrapping process. Furthermore, differences on the dipole potential caused by DXI-NPs in each corneal membrane have been obtained due to the increase of membrane rigidity on the ECMM. Additionally, it can be confirmed that DXI-NPs adhere to Lo phase and also inside the lipid membrane. Finally, in vitro and in vivo results corroborate that DXI-NPs are adhered to the more ordered phase. Finally, differences between interactions of DXI-NPs with the elder and adult corneal tissue were observed., The authors want to acknowledge the support of the Spanish Ministry under the project PID2021-122187NB-C32 and the support of the Generalitat of Catalonia (2017SGR1447). ESL wants to acknowledge the support of the Grants for the Requalification of the Spanish University System and the Institute of Nanoscience and Nanotechnology (ART2018 project). GE, acknowledges the financial support of the Generalitat de Catalunya for the PhD scholarship FI-SDUR (2020FISDU187). The authors also acknowledge the student Roberto Rocamora for his technical support. The authors would like to thank Manel Bosch Marimón from the Scientific and Technological Center of the University of Barcelona for his technical support.

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.

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., This work was supported by Wrocław University of Environmental and Life Sciences (Poland) under the Leading Research Groups support project from the subsidy increased for the period 2020–2025 in the amount of 2% of the subsidy referred to Art. 387 (3) of the Law of 20 July 2018 on Higher Education and Science, obtained in 2019. E.S.-L. want to acknowledge the support of the Grants for the Requalification of the Spanish University System. The authors M.E., M.L.G. and E.S.-L. want to acknowledge the Spanish Ministry of Science and Innovation (project reference PID2021-122187NB-C32).

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.

Pain is an unpleasant sensory and emotional sensation associated with tissue damage or described in terms of such damage. Pain of different localization is one of the most common symptoms in modern clinical practice and one of the most common reasons for seeking medical care at the outpatient stage. One of the most promising and effective pathogenetic means of protection of peripheral pain receptors (nociceptors) are nonsteroidal anti-inflammatory drugs (NSAIDs). Every day, more than 30 million people in the world take NSAIDs, more than 300 million a year, and only a third of them take nonsteroidal anti-inflammatory drugs as prescribed by a doctor. However, patients taking various drugs today are considered as possible etiological and provoking factors in the development of a number of diseases of various organs and systems. All this determines the importance of selecting the optimal drug from the group of nonsteroidal anti-inflammatory drugs both from the standpoint of effectiveness and from the standpoint of safety in real clinical practice and including at the outpatient stage of providing medical care to the patient. One of the latest developments in this direction is dexibuprofen, the right-handed active isomer of ibuprofen, which according to numerous studies can be used as a symptomatic therapy of pain of mild to moderate intensity of various origins: toothache, back pain, joints, muscles, rheumatic pain, dysmenorrhea, and feel free to recommend it to a wide range of patients, as it has the optimal combination of efficacy and safety profile.

El descubrimiento del ibuprofeno tiene su origen en el año 1953 a raíz de la búsqueda de análogos del ácido acetilsalicílico, con el objetivo de encontrar un fármaco más seguro y eficaz. Tras una serie de experiencias fallidas, se logró obtener el ácido 2-4-isobutil-fenil-propiónico o ibuprofeno, cuya potencia antiinflamatoria y baja hepatotoxicidad, llevó a la molécula a ser rápidamente comercializada. Hoy en día constituye un eslabón clave de la “escalera analgésica” siendo utilizado por millones de personas alrededor del mundo. En este trabajo se ha realizado un estudio de las fichas técnicas de los medicamentos que contienen ibuprofeno en su formulación recogidos en la Agencia Española de Medicamentos y Productos Sanitarios a fecha de noviembre de 2021, obteniéndose información sobre diferentes aspectos de estos medicamentos: forma farmacéutica, vía de administración, formulación y dosis, entre otros. Los pacientes encuentran en el mercado español un elevado número de especialidades, en concreto, 166 de administración mayoritariamente oral (143), aunque también las hay tópicas (16) y parenterales (7). En las orales, la formación de sales con L-arginina, lisina, complejación con β-ciclodextrina, o formulación en forma de cápsulas blandas, son diferentes estrategias para incrementar la rapidez del inicio de la acción. The discovery of ibuprofen was originated in 1953 as a result of the research for analogs of acetylsalicylic acid, to find a safer and more effective drug. After a series of unsuccessful experiences, it was possible to obtain 2-4-isobutyl-phenyl-propionic acid or ibuprofen, whose anti-inflammatory potency and low hepatotoxicity led the molecule to be quickly commercialized. Today it constitutes a key link on the “analgesic ladder” being used by millions of people around the world. In this work, an investigation has been carried out of the technical specifications of the medicines that contain ibuprofen in their formulation collected in the Spanish Agency for Medicines and Health Products in November 2021. Information was obtained on different aspects of these drugs: pharmaceutical form, route of administration, formulation, and dose, among others. Patients can find a large number of medicines in the Spanish market, specifically 166 of mostly oral administration (143), although there are also topical (16) and parenteral (7). In oral administration, the formation of salts with L-arginine, lysine, complexation with β-cyclodextrin, or formulation in the form of soft capsules, are different strategies to increase the speed of onset of action.

The intention of the current study was to investigate the Physico-chemical characteristics of Dexibuprofen loaded nanoparticles. Dexibuprofen is an NSAID - non-steroidal anti-inflammatory drug intended for the treatment of rheumatoid arthritis related symptoms. In current market trends, the tablets and capsule dosage forms captures major market contribution. A systematic evaluation of physico chemical characteristics of the drug powder, it’s characteristics was performed as a basic step at the start of formulation development of the dosage form. The formulation development approach is decided based on the above data. Dexibuprofen nanoparticles was developed by an Ionotropic pre gelation technique comprising Chitosan, Calcium chloride and Sodium alginate as coating material. The preformulation evaluation of Dexibuprofen and it’s compatibility with selected excipients was performed to design an appropriate strategy for the development of Dexibuprofen modified release nanoparticles. The parameters like melting point, pKa, solubility, dissolution and assay method development, solid state stability, solution stability, flow properties, bulk density, microscopical assessment, entrapment efficiency, excipients compatibility, and nanoparticles release profile were evaluated. The results of this study, along with the experimental values, will be discussed in detail.

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 ...

Objectives In this communication we report an important findings, the effect of Al/Mg hydroxide antacid and food on the pharmacokinetics of dexibuprofen when administered concomitantly. Methods Subjects were divided into four groups, each containing 6 subjects, to evaluate the effect of antacid and food on pharmacokinetic of dexibuprofen. A new HPLC method was developed and validated for plasma sample analysis. Mobile phase was comprised of Acetonitrile: Methanol: 0.05M Phosphate buffer (40:10:50), pH was adjusted to 6.85±0.01 with NaOH. Mobile phase was eluted through C18-ODS column and drug was detected at 223 nm. Plasma was obtained and stored at − 70°C until analysis. Drug was extracted from each plasma sample of volunteer and quantified by using HPLC technique. Results A decrease in dexibuprofen absorption was observed in Test Group-1 when administered with Antacid as compared to Controlled Group-1. Mean Cmax values showed a significant (p value 0.035) decrease from 44.14±2.3 to 33.1±0.8 μg/mL. Tmax, Area under curve, t1/2, Cl, Vd and Ke were not affected significantly. AUC increased from 195.7±8.9 μg.hr/mL to 222.8±14.7 μg.hr/mL. In contrast, test Group-2 showed an increase in dexibuprofen absorption. t1/2 increased significantly from 4.505±0.19 hrs to 6.216±0.36 hrs whereas Ke reduced from 0.159±0.00 to 0.116±0.006 hrs-1. Cmax increased from 44.877±2.263 to 51.721±0.096 μg/mL. Conclusion It is concluded that concomitant intake of Al/Mg hydroxide antacid or food with dexibuprofen has an impact to significantly alter its pharmacokinetic parameters.

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.

Background The amide derivatives of nonsteroidal anti-inflammatory drugs have been reported to possess antitumor activity. The present work describes the synthesis of dexibuprofen amide analogues (4a-j) as potential anticancer agents. Methods The title amides (4a-j) were obtained by simple nucleophilic substitution reaction of dexibuprofen acid chloride with substituted amines in good yield and chemical structures were confirmed by FTIR, 1H NMR, 13C NMR and mass spectral data. Results The brine shrimp lethality assay results showed that all of the synthesized compounds are non-toxic to shrimp larvae. The inhibitory effects on tumor growth were evaluated and it was observed that N-(2,5-dichlorophenyl)-2-(4-isobutylphenyl) propionamide (4e) and N-(2-chlorophenyl)-2-(4-isobutylphenyl) propionamide (4g) exhibited excellent antitumor activity compared to all other derivatives. The compound 4e bearing 2,5-dichloro substituted phenyl ring and 4g possesses 2-chloro substituted phenyl ring exhibited 100% inhibition of the tumor growth. The anticancer activity was evaluated against breast carcinoma cell line (MCF-7) and it was observed that derivative 4e exhibited excellent growth inhibition of cancer cells with IC50 value of 0.01±0.002 µm, which is better than the standard drugs. The docking studies against breast cancer type 1 susceptibility protein BRCA1 (PDBID 3K0H) exhibited good binding affinities, which are in good agreement with the wet lab results. The compounds 4e and 4g showed the binding energy values of -6.39 and -6.34 Kcal/mol, respectively. The molecular dynamic (MD) simulation was also carried out to evaluate the residual flexibility of the best docking complexes of compounds 4e and 4g. The MD simulation analysis assured that the 4e formed a more stable complex with the target protein than the 4g. The synthesized amide derivatives exhibited were devoid of gastrointestinal side effects and no cytotoxic effects against human normal epithelial breast cell line (MCF-12A) were found. Conclusion Based upon our wet lab and dry lab findings we propose that dexibuprofen analogue 4e may serve as a lead structure for the design of more potent anticancer drugs.

Pain is an unpleasant sensory and emotional sensation associated with tissue damage or described in terms of such damage. Pain of different localization is one of the most common symptoms in modern clinical practice and one of the most common reasons for seeking medical care at the outpatient stage. One of the most promising and effective pathogenetic means of protection of peripheral pain receptors (nociceptors) are nonsteroidal anti-inflammatory drugs (NSAIDs). Every day, more than 30 million people in the world take NSAIDs, more than 300 million a year, and only a third of them take nonsteroidal anti-inflammatory drugs as prescribed by a doctor. However, patients taking various drugs today are considered as possible etiological and provoking factors in the development of a number of diseases of various organs and systems. All this determines the importance of selecting the optimal drug from the group of nonsteroidal anti-inflammatory drugs both from the standpoint of effectiveness and from the standpoint of safety in real clinical practice and including at the outpatient stage of providing medical care to the patient. One of the latest developments in this direction is dexibuprofen, the right-handed active isomer of ibuprofen, which according to numerous studies can be used as a symptomatic therapy of pain of mild to moderate intensity of various origins: toothache, back pain, joints, muscles, rheumatic pain, dysmenorrhea, and feel free to recommend it to a wide range of patients, as it has the optimal combination of efficacy and safety profile., Боль – неприятное сенсорное и эмоциональное ощущение, связанное с повреждением ткани или описанное в терминах такого повреждения. Именно боль различной локализации является одним из самых распространенных симптомов в клинической практике и одной из наиболее частых причин обращения за медицинской помощью на амбулаторно-поликлиническом этапе. Одним из наиболее перспективных и действенных патогенетических средств защиты периферических болевых рецепторов (ноцицепторов) являются нестероидные противовоспалительные препараты (НПВП). Ежедневно в мире более 30 млн человек принимают НПВП, за год – более 300 млн человек, при этом только треть из них принимают нестероидные противовоспалительные средства по назначению врача. Однако применение пациентами различных лекарственных препаратов на сегодняшний день рассматривается в качестве возможных этиологических и провоцирующих факторов развития целого ряда заболеваний различных органов и систем. Все это обусловливает важность подбора оптимального препарата из группы нестероидных противовоспалительных средств как с позиций эффективности, так и с позиции безопасности в реальной клинической практике и в том числе на амбулаторно-поликлиническом этапе оказания пациенту медицинской помощи. Одна из последних разработок в этом направлении – дексибупрофен, правовращающий активный изомер ибупрофена, который по данным многочисленных исследований можно применять в качестве симптоматической терапии боли слабой и умеренной интенсивности различного происхождения: зубной боли, боли в спине, суставах, мышцах, ревматической боли, дисменореи, и смело рекомендовать широкому кругу пациентов, поскольку препарат имеет оптимальное сочетание профиля эффективности и безопасности., Біль – неприємне сенсорне й емоційне відчуття, пов’язане з пошкодженням тканини або описане в термінах такого ушкодження. Саме біль різної локалізації є одним із найбільш поширених симптомів у сучасній клінічній практиці й однією з найбільш частих причин звернення за медичною допомогою на амбулаторно-поліклінічному етапі. Одним із найбільш перспективних і дієвих патогенетичних засобів захисту периферичних больових рецепторів (ноцицепторов) є нестероїдні протизапальні препарати (НПЗП). Щодня у світі понад 30 млн осіб приймають НПЗП, за рік – понад 300 млн осіб, при цьому лише третина з них вживають нестероїдні протизапальні засоби за призначенням лікаря. Однак вживання пацієнтами різних лікарських препаратів на сьогодні розглядається в якості можливих етіологічних і провокуючих чинників розвитку цілої низки захворювань різних органів і систем. Усе це зумовлює важливість підбору оптимального препарату з групи нестероїдних протизапальних засобів як з позицій ефективності, так і з позиції безпеки в реальній клінічній практиці і зокрема на амбулаторно-поліклінічному етапі надання пацієнтові медичної допомоги. Однак несприятливі побічні ефекти характерні практично для всіх представників групи нестероїдних протизапальних засобів (з різною частотою) незалежно від їхнього хімічного складу, лікарської форми і способу введення. Саме тому на сьогодні безпека застосування є одним із пріоритетних напрямків сучасної медицини і фармації. Одна з останніх розробок у цьому напрямку – дексібупрофен, правообертальний активний ізомер ібупрофену, який за даними численних досліджень можна застосовувати в якості симптоматичної терапії болю слабкої та помірної інтенсивності різного походження: зубного болю, болю у спині, суглобах, м’язах, ревматичного болю, дисменореї, та сміливо рекомендувати широкому колу пацієнтів, оскільки препарат має оптимальне поєднання профілю ефективності та безпеки.

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. View Full-Text Keywords: dexibuprofen; NSAIDs; enantiomer; drug delivery; prodrugs

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.

Electrophoresis : microfluids & proteomics 10, (2021). doi:10.1002/elps.202000307, Published by Wiley-Blackwell, Weinheim

Transdermal application of analgesics allows efficient and painless delivery of medication with minimum side effect. This study was designed with the aim to formulate and characterize dexibuprofen-capsaicin emulgel for transdermal drug delivery with improved anti-inflammatory and analgesic effects. The emulgel was prepared and evaluated for physical examination, stability, spreadability, rheological behavior, viscosity, drug content determination, FTIR analysis, and ex vivo studies. Anti-inflammatory (carrageenan-induced paw edema) and analgesic (hot plate latency test) effects were determined in Sprague-Dawley rats. The dexibuprofen-capsaicin emulgel showed good physical appearance and stability having average pH 5.5 to 6.0, conductivity 73–76 s/m, spreadability (12–)17 g cm/s, drug content 102.84% ± 0.53 (for capsaicin) and 94.09% ± 0.41 (for dexibuprofen), and FTIR compatibility. It was noted that 86.956% ± 1.46 (with 100 mg menthol), 76.687% ± 1.21 (75 mg menthol), and 65.543% ± 1.71 (without menthol) of capsaicin were released. Similarly 81.342% ± 1.21 (with 100 mg menthol), 72.321% ± 1.31 (75 mg menthol), and 52.462% ± 1.23 (without menthol) of dexibuprofen were released. The cumulative amount of capsaicin permeated through rabbit skin was 9.83 ± 0.037 μg/cm2 with 100 mg menthol (as permeation enhancer), 7.23 ± 0.037 μg/cm2 with 75 mg menthol, and 2.23 ± 0.061 μg/cm2 without menthol after 6.5 h. The permeation of dexibuprofen was 19.53 ± 0.054 μg/cm2, 13.87 ± 0.032 μg/cm2, and 3.83 ± 0.074 μg/cm2. Carrageenan-induced paw edema of rat was effectively inhibited by the optimized emulgel. Similarly it was observed that DCE5 shows higher analgesic activity compared with marketed diclofenac sodium emulgel (Dicloran®). The conclusion of this research study evidently indicated a promising synergistic potential of dexibuprofen-capsaicin emulgel as an alternative to the conventional topical dosage form.

Background Fever is one of the most common symptoms in children and is the physiological response of the human immune system to external pathogens. However, effectiveness studies of single and combined antipyretic therapy are relatively few due to lack of data. In this study, we used large-scale patient-generated health data from mobile apps to compare antipyretic affects between single and combination antipyretics. Objective We aimed to establish combination patterns of antipyretics and compare antipyretic affects between single and combination antipyretics using large-scale patient-generated health data from mobile apps. Methods This study was conducted using medical records of feverish children from July 2015 to June 2017 using the Fever Coach mobile app. In total, 3,584,748 temperature records and 1,076,002 antipyretic records of 104,337 children were analyzed. Antipyretic efficacy was measured by the mean difference in the area under the temperature change curve from baseline for 6 hours, 8 hours, 10 hours, and 12 hours after antipyretic administration in children with a body temperature of ≥38.0 ℃ between single and combination groups. Results The single antipyretic and combination groups comprised 152,017 and 54,842 cases, respectively. Acetaminophen was the most commonly used single agent (60,929/152,017, 40.08%), and acetaminophen plus dexibuprofen was the most common combination (28,065/54,842, 51.17%). We observed inappropriate use, including triple combination (1205/206,859, 0.58%) and use under 38 ℃ (11,361/206,859, 5.50%). Combination antipyretic use increased with temperature; 23.82% (33,379/140,160) of cases were given a combination treatment when 38 ℃ ≤ temperature < 39 ℃, while 41.40% (1517/3664) were given a combination treatment when 40 ℃ ≤ temperature. The absolute value of the area under the curve at each hour was significantly higher in the single group than in the combination group; this trend was consistently observed, regardless of the type of antipyretics. In particular, the delta fever during the first 6 hours between the two groups showed the highest difference. The combination showed the lowest delta fever among all cases. Conclusions Antipyretics combination patterns were analyzed using large-scale data. Approximately 75% of febrile cases used single antipyretics, mostly acetaminophen, but combination usage became more frequent as temperature increased. However, combination antipyretics did not show definite advantages over single antipyretics in defervescence, regardless of the combination. Single antipyretics are effective in reducing fever and relieving discomfort in febrile children.

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., This work was supported by grant RTI2018-094120-B-I00 from the Spanish Ministry of Economy, Industry and Competitiveness (MINECO) and the European Regional Development Fund. ESL wants to acknowledge the Institute of Nanoscience and Nanotechnology (ART2018 project)., info:eu-repo/semantics/publishedVersion

We compared the fever-reducing efficacy of acetaminophen (AA), ibuprofen (IBU), and dexibuprofen (DEX) using data collected from the mobile healthcare application FeverCoach, which provides parents with guidelines for determining their child’s health condition, according to body temperature. Its dataset includes 4.4 million body temperature measurement records and 1.6 million antipyretics treatment records. Changes in body temperature over time were compared after taking one of three different antipyretics (AA, IBU, and DEX), using a one-way ANOVA followed by a post-hoc analysis. A multivariate linear model was used to further analyze the average body temperature differences, calibrating for the influences of age, weight, and sex. Children administered IBU had average body temperatures that were 0.18 °C (0.17–0.19 °C), 0.25 °C (0.24–0.26 °C), and 0.18 °C (0.17–0.20 °C) lower than those of children administered AA, at time intervals of 1–2 hours, 2–3 hours, and 3–4 hours, respectively. Similarly, children administered DEX had average body temperatures that were 0.24 °C (0.24–0.25 °C), 0.28 °C (0.27–0.29 °C), and 0.12 °C (0.10–0.13 °C) lower than those of children administered AA, at time intervals of 1–2, 2–3, and 3–4 hours, respectively. Although the data were collected from the application by non-professional parents, the analysis showed that IBU and DEX were more effective in reducing body temperature than AA was.

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 (AUC0–24) and mean residence time (MRT0–24) were 644.49 ± 73.26 μg/h/mL and 7.65 ± 0.48 h, both of which were significantly larger than commercial IBU suspension (AUC0–24 of 439.88 ± 84.41 μg/h/mL and MRT0–24 of 3.10 ± 0.38 h), respectively (P

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±2.5nm and 90±3.0nm, 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±3.5µg/mL compared to the raw Dexi in water (51.0±2.0µg/mL) and stabilizer solution (92.0±3.0µg/mL). Enhanced dissolution rate (P

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.

The purpose of this study was to use hydroxypropyl-β-cyclodextrin (HP-β-CD) as a novel carrier in solid SNEDDS and solid dispersions to enhance the solubility and oral bioavailability of poorly water-soluble dexibuprofen. The novel dexibuprofen-loaded solid SNEDDS was composed of dexibuprofen, corn oil, polysorbate 80, Cremophor® EL, and HP-β-CD at a weight ratio of 45/35/50/15/100. This solid SNEDDS spontaneously formed a nano-emulsion with a size of approximately 120 nm. Unlike the conventional solid SNEDDS prepared with colloidal silica as a carrier, this dexibuprofen-loaded solid SNEDDS exhibited a spherical structure. Similar to the dexibuprofen-loaded solid dispersion prepared with HP-β-CD, the transformation of the crystalline drug to an amorphous state with no molecular interactions were observed in the solid SNEDDS. Compared to the solid dispersion and dexibuprofen powder, solid SNEDDS significantly enhanced drug solubility and AUC. Therefore, HP-β-CD is a novel potential carrier in SNEDDS for improving the oral bioavailability of dexibuprofen.

A novel prodrug approach was undertaken to develop the safe and therapeutically efficacious dexibuprofen to avoid oral NSAIDs induced ulceration. Dexibuprofen was esterified with dextran, using N,N-carbonyldiimidazole in one pot reaction. Synthesized dexibuprofen prodrug was characterized and evaluated by FT-IR and NMR spectroscopy, molecular weight, lipophilicity, partition coefficient, protein binding, degree of substitution, hydrolysis in simulated GI fluids, in-silico ADME properties and pharmacological potentials. Structural profile of dexibuprofen prodrug was elucidated by an ester linkage, glucosidic ring anomeric proton, dextran monomer protons and ester carbonyl carbon signals. Prodrug possessed physicochemical features as molecular weight of 83,368.11 g/mol, log P of 5.4 with optimal protein binding of 66% and degree of substitution of 25.3%. It was significantly hydrolyzed in SIF (99.53%) by following first-order kinetics with 85.9 min half-life. In-silico ADME properties of prodrug satisfied the Lipinski' rule of five and Jorgensen's rule of three without any CNS activity and cardiac toxicity, thus prodrug was suitable for oral administration. Prodrug has exhibited superior analgesic, anti-inflammatory, antipyretic activities devoid of antigenecity and ulceration in experimental animals. Data of the study were thus evinced that dexibuprofen prodrug is a safer therapeutic moiety in effective management of acute inflammation, pain and fever.

The purpose of this study was to develop and characterize hydroxypropyl-β-cyclodextrin (HPβCD) hybrid nanogels for solubility enhancement of lipophilic drug, dexibuprofen. HPβCD hybrid nanogels were designed by chemical cross-linking of hydroxypropyl-β-cyclodextrin with 2-acrylamido-2-methyl propane sulfonic acid (AMPS) via free radical polymerization. Loading efficiency, solubilization, zetasizer, FESEM Fourier transform infrared (FTIR), differential scanning calorimetry (DSC), thermal gravimetric analysis (TGA), powder X-ray diffraction (PXRD), and in vitro drug release analysis were performed for characterization of hybrid nanogels. Efficient solubilization of dexibuprofen has been observed by HPβCD hybrid nanogels. FTIR, TGA, and DSC studies confirmed the formation of new hybrid nanogels and complexation of dexibuprofen with nanogels. XRD analysis revealed loss of dexibuprofen crystallinity in hybrid nanogels. Highly porous and amorphous nanogels showed a significant dexibuprofen release in aqueous medium. In toxicity studies, no significant changes in behavioral, physiological, biochemical, or histopathological parameters of animals endorsed that developed formulations are nontoxic and biocompatible.

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.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.βCD hydrogel nanoparticles were prepared and characterized by percent yield, drug loading, solubilization efficiency, FTIR, XRD, DSC, FESEM and in-vitro dissolution studies. Acute oral toxicity study was conducted to assess safety of oral administration of prepared βCD hydrogel nanoparticles.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.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.

This study was designed to enhance solubility of dexibuprofen, an NSAID drug used to treat moderate to severe pain, by fabricating first generation, carbonate type nanosponges of β-CD. Novel chain-growth polycondensation method was used for the first time for preparation of the β-CD nanosponges. The results exhibited 6.3-fold enhancement of dexibuprofen solubilization which is higher than previously reported β-CD formulations. The particle size of nanosponges was 275.1 ± 28.5 nm and suitable negative zeta potential indicated formation of stable nanosponges. The formation of a new polymeric network in nanosponges and interaction of dexibuprofen with nanosponges were confirmed by FTIR and DSC/TGA studies. PXRD analysis also revealed the decline in crystallinity of dexibuprofen due to its complexation with nanosponges which is desirable for complete solubilization of drugs. At pH 6.8, β-CD nanosponges exhibited swelling index of 3 whereas solubility was enhanced more than 3 times as compared to pure drug and 2 times as compared to dexibuprofen loaded β-CD complexes. In-vitro release studies exhibited 89% drug release within 30 min at pH 6.8 with β-CD nanosponges. Dexibuprofen release at pH 1.2 was remarkably slower yet β-CD nanosponges showed superior dissolution as compared to β-CD or pure drug. Acute oral toxicity studies in rats exhibited no sign of illness, mortality, adverse clinical signs and toxicologically relevant changes in hematology, clinical biochemistry and histological findings. Thus, β-CD nanosponges prepared by optimized condensation method may be superior to other nano-formulation of β-CD to improve oral administration of lipophilic drugs such as dexibuprofen.

Traditional dosage forms of dexibuprofen extremely limit their clinical applications because of the bitter taste and the frequent drug administration caused by the relatively short half-life of the drug. This study aims to design novel sustained release (SR) supermicro-pellet based dry suspensions that load dexibuprofen, and also optimize the formulations in terms of morphology, release rate, flowability, and physicochemical stability of dosage forms. Drug-loaded pellets were prepared by using a bottom spray fluid bed coating technique using microcrystalline cellulose supermicro-pellets as the core and PVP K30 or Poloxamer 188 as the binder. The drug-loaded pellets were further coated with Kollicoat SR 30D to form SR pellets. The optimal SR dry suspensions are composed of SR pellets, diluent granules, and suspending agents. PVP K30- and Poloxamer 188-based SR pellets release the drug molecules in a SR manner over 8 h and show a high release profile for Poloxamer 188-based pellets. The drug release profile is not affected by the rotation speed of the paddle but shows a distinct pH-responsive behavior. The physical property of dexibuprofen has been changed during the preparation process. The SR dry suspensions (F5, with high amount of xanthan gum in suspending agents and low amount of poloxamer 188 in diluent granules) show high physical stability with the sedimentation rate of 0.8 (Hu/H) within 5 min and good flowability with the angle of repose (θ) at 27°. Low content variations were observed with a value of A+1.80SD ≤ 15, and no significant change was found in the drug content under high humidity and strong light. In conclusion, novel SR supermicro-pellet based dry suspensions have been successfully prepared, and the optimal formulation shows excellent SR, good flowability, content uniformity, and physicochemical stability.

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, DÄ«r, 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 diffractionconfirmed 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

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.

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±2.5nm and 90±3.0nm, 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±3.5µg/mL compared to the raw Dexi in water (51.0±2.0µg/mL) and stabilizer solution (92.0±3.0µg/mL). Enhanced dissolution rate (P

Dexibuprofen is a practically water-insoluble nonsterodial anti-inflammatory drug. Following previous experience on enhancing the solubility of the drug, a mixed hydrotropic solubilization technique was here applied in order to improve the aqueous solubility of the drug so that a soluble form of dexibuprofen was prepared and then could be used as a main active ingredient in transdermal films. Nine formulae were prepared applying 32 full factorial design using different amounts of hydroxypropylmethylcellulose (HPMC) and polyvinylpyrrolidone K30 (PVP K30). The prepared formulae were evaluated for their physical properties, loading efficacy and In-vitro dissolution studies adopting the USP XXII dissolution method type V paddle over disk apparatus method. Permeation studies were done for best three films showing higher dissolution rate using Franz cell apparatus and also bioavailability study was carried out on the best formula to compare the absorption of dexibuprofen from the prepared film (treatment A) to commercial tablets (treatment B) following administration of a single dose to rabbits. The prepared films were off-white color, opaque, smooth, moist and non-sticky. Increasing the amounts of HPMC and PVP K30 lead to increasing weight, folding endurance, tensile strength, moisture content and moisture absorption. Transdermal films containing higher concentrations of PVP K30 and lower concentration of HPMC showed higher rate and amount of dexibuprofen released from dissolution medium and Franz cell. The bioavailability study showed that (Tmax) in treatments A and B is 3 hours and 2 hours respectively. The average peak plasma concentration values (Cmax) were 28.98±3.36 and 34.67±0.61 ug/mL, respectively and the AUC0-∞ values were 145.82±13.09 and 117.44±3.15 µg·h/mL, respectively. There were significant differences between treatments A and B in Cmax, t(1/2)ab, Kel, t(1/2)el, TCR, AUC0-8, AUC0-∞, AUMC0-8, AUMC0-∞, and MRT. While the difference was insignificant in Kab.

The aim of the study was to develop a reservoir-type transdermal patch for a controlled delivery of dexibuprofen and to evaluate its in vivo anti-inflammatory activity in Albino Wistar rats. In order to develop these patches, six formulations of dexibuprofen microemulsion comprising ethyl oleate, Tween 80: PG (2 : 1), and water were prepared by simplex lattice design and characterized. The reservoir compartment was filled with these microemulsions and in vitro release and skin permeation were assessed. The optimized patch was obtained on the basis of the responses:Q24and flux. The impact of drug loading, surface area, membrane thickness, adhesive, and agitation speed on drug release and permeation was also studied. The skin sensitivity reaction and in vivo anti-inflammatory activity of optimized patch were evaluated. Stability study at three different temperatures for three months was carried out. The result suggests that a membrane based patch with zero-order release rate,Q24of 79.13 ± 3.08%, and maximum flux of 331.17 µg/cm2h can be obtained exhibiting suitable anti-inflammatory activity with no visible skin sensitivity reaction. The outcomes of stability study recommend storage of patches at 4°C having shelf-life of 6.14 months. The study demonstrates that the reservoir-type transdermal patch of dexibuprofen microemulsion has a potential of delivering drug across skin in controlled manner with required anti-inflammatory activity.

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., Graphical abstract fx1, Highlights • DXI treatment improves cognitive impairment in APPswe/PS1dE9 mice through multiple targets. • Aβ reduction occurs with DXI inhibiting APP, BACE1 and increasing IDE1 hippocampal protein levels. • DXI contributes to TAU hyperphosphorylation decreasing but does not alter total TAU expression. • CDK5 pathway is altered by DXI inhibiting CDK5 phosphorylation via TNFα/c-ABLl/CABLES. • DXI decreases pAKT/pGSK3β protein levels which are involved in insulin signaling pathway.

Postoperative pain may lead to poor wound healing, insomnia, and increased postoperative hospitalization. The objective of the study was to explore the effect of local infiltration of the surgical wound with levobupivacaine, dexibuprofen, and norepinephrine in postoperative pain. A randomized, parallel experimental design was applied in 40, 9-11-week-old Wister albino rats. A laparotomy was performed in all groups of 10 rats each. During surgery, the sutured muscle was infiltrated with 40μL of a normal saline (vehicle group), a normal saline containing 0.25% v/v levobupivacaine, 0.2mg/mL dexibuprofen, and 0.1mg/mL norepinephrine (treatment group) before skin closure. The same combination (negative control group) and a 10-fold higher dose (positive control group) were administered systematically. Rat Grimace Scale scores, based on facial expression, 24h after suturing of the tissues, histopathology and tensile strength of the surgical wound, two weeks after suturing of the tissues were measured. The one-way ANOVA and the two-tailed paired t-test/the Dunnett multiple comparisons test were used to compare the Rat Grimace Scale scores for pain within the group and between groups. The Kruskal-Wallis test and the one-way ANOVA/the Dunnett multiple comparisons test were used to compare the histopathology study and the tensile strength. The difference for statistical analysis was considered significant at the 95% of confidence level. The mean Rat Grimace Scale score at 24h for the treatment, negative control, and positive control groups was 1.945 (p=0.0025; q=3.257), 1.1 (p=0.1), and 1.95 (p=0.0021 q=3.547) respectively. The reduction in postoperative pain started within 1h after the suturing of the tissues in the treatment group. There were significant difference for epidermal and dermal regeneration (p=0.043), granulation tissue thickness (p=0.025), and angiogenesis (p=0.002) between treatment group and vehicle group. Tensile strength for the treatment group was 0.82±0.013N/cm2(p=0.003; q=5.231). The rapid infiltration of surgical wounds with a low-dose levobupivacaine, dexibuprofen, and norepinephrine may reduce postoperative pain and increase the wound regeneration process.

D exibuprofen is a poorly water soluble nonsteroidal anti - inflammatory drug, prescribed for moderate to severe p ain and inflammation. It is the active dextrorotatory enantiomer of ibuprofen and has better anti - in flammatory effect . Hence present study was carried out to enhance dissolution properties of dexibuprofen through the preparation of solid lipid nano particl es (SLNPs) using stearic acid as lipid, lutrol F - 68 (Poloxamer) as surfactant and tween - 80 as stabilizer by hot homogenization method. Six formulations were prepared in different ratios and were designated as DNP1 to DNP6 . USP type II rotating paddle disso lution studies in 900 ml distilled water at 50 rpm to a temperature of 37°C ± 0.5°C were performed for evaluation of solid lipid nano particles. UV s pectrophotometric method was selected for assay as well as in - vitro dissolution studies at λ max 222 nm. The drug release profil e followed zero order and first order kinetics. In - vitro studies showed that solubility and dissolution rate of dexibuprofen were significantly improved by SLN formulation than the d rug alone . This result may trigger mor e research in the intension of exploiting this feature to develop a novel drug delivery system for dexibuprofen with enhanced bioavailability.

The optical purity of 11 commercial dexibuprofens and 7 ibuprofens sold in Korea in 2013 were examined by chiral HPLC. The Chiralcel OD-H column and LUX-Cellulose-1 column were used as chiral stationary phases and the mixed eluent of hexane:isopropanol:acetic acid as 100:1:0.1 was used as a mobile phase with a flow rate of 1.0 mL/min. Each data was obtained from an average value of at least three different experiments for each sample and the average value of relative standard deviation of them appeared very small, 0.19%. Average optical purity value (97.5%) of eleven commercial dexibuprofens used in this study were smaller than those of 9 years ago (99.2%), but larger than four years ago (95.6%). Enantiomeric ratios of (R)- and (S)- isomers of seven ibuprofen samples used in this experiment were achieved at about 50:50 which was different with the result (44:56) from four years ago.

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.

Objective: To evaluate the role of anti-depressants (Duloxetine) and NSAID (Dexibuprofen) in a new rat model of chronic induced depression. Methods: Twenty four male wistar rats were divided into 4 groups of 6 animals each. Group I to IV served as vehicle control, osteoarthritis (OA) control, duloxetine and dexibuprofen treated groups respectively. Group I received intra-articular Injection of 50 µl of 0.9% normal saline, and Group II to IV received 50 µl MIA, and the treatment of drugs started on the same day. The animals will be monitored for OA parameters and/or depression on pre-dose day (day 0) and on day 1, 3, 5, 7, 11, 14, 18, 21 and 28 th day. Results and Discussion: In MIA treated group, the rise in knee inflammation is maximum on day 3 (12.31±0.85 mm; p

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.

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

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.

The presence of free carboxylic acid group in majority of non-steroidal anti-inflammatory drug (NSAIDs) is responsible from GI irritation. Coupling of the appropriate NSAIDs (diclofenac, naproxen, dexibuprofen and meclofenamic acid) 1 – 4 , respectively with the appropriate amino acid ester 5 using dicyclohexylcarbodiimide afforded prodrugs 6 – 13 . The structures of the prodrugs were verified based on spectral data. Chemical hydrolysis studies performed in three different non enzymatic buffer solutions at pH 1.2, 5.5 and 7.4, as well as in 80% human plasma and 10% rat liver homogenate using HPLC indicate no conversion of prodrugs to their respective NSAID in the studied buffers, while they underwent a reasonable plasma and rat liver homogenate hydrolysis. Furthermore, ulcerogenicity of prodrugs 9 and 12 were studied and results revealed no gastro-ulcerogenic effects.

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.

Dexibuprofen-loaded PEGylated PLGA nanospheres have been developed to improve the biopharmaceuti-cal profile of the anti-inflammatory drug for ocular administration. Dexibuprofen is the active enantiomerof ibuprofen and therefore lower doses may be applied to achieve the same therapeutic level. Accordingto this, two batches of nanospheres of different drug concentrations, 0.5 and 1.0 mg/ml respectively, havebeen developed (the latter corresponding to the therapeutic ibuprofen concentration for inflammatoryeye 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 DSCanalyses confirmed that the drug was dispersed inside the matrix of the nanospheres. While the in vitrorelease profile was sustained up to 12 h, the ex vivo corneal and scleral permeation profile demonstratedhigher drug retention and permeation in the corneal tissue rather than in the sclera. These results werealso confirmed by the quantification of dexibuprofen in ocular tissues after the in vivo administration ofdrug-loaded nanospheres. Cell viability studies confirmed that PEGylated-PLGA nanospheres were lesscytotoxic than free dexibuprofen in the majority of the tested concentrations. Ocular in vitro (HET-CAMtest) and in vivo (Draize test) tolerance assays demonstrated the non-irritant character of both nanospherebatches. In vivo anti-inflammatory effects were evaluated in albino rabbits before and after inflammationinduction. Both batches confirmed to be effective to treat and prevent ocular inflammation. Keywords: Nanospheres, Dexibuprofen, PLGA, PEG, Inflammation, Drug delivery