Spectrophotometric determination of celecoxib and tramadol in the new approved formulated dosage form using principle component regression assistive model.

Celecoxib and tramadol have been combined in a novel FDA-approved medication to address acute pain disorders requiring opioid treatment when other analgesics proved either intolerable or ineffective. The absorbance spectra of celecoxib and tramadol exhibit significant overlap, posing challenges for their individual quantification. This study introduces a spectrophotometric quantification approach for celecoxib and tramadol using a principle component regression assistive model to assist resolving the overlapped spectra and quantifying both drugs in their binary mixture. The model was constructed by establishing calibration and validation sets for the celecoxib and tramadol mixture, employing a five-level, two-factor experimental design, resulting in 25 samples. Spectral data from these mixtures were measured and preprocessed to eliminate noise in the 200-210 nm range and zero absorbance values in the 290-400 nm range. Consequently, the dataset was streamlined to 81 variables. The predicted concentrations were compared with the known concentrations of celecoxib and tramadol, and the errors in the predictions were evidenced calculating root mean square error of cross-validation and root mean square error of prediction. Validation results demonstrate the efficacy of the models in predicting outcomes; recovery rates approaching 100 % are demonstrated with relative root mean square error of prediction (RRMSEP) values of 0.052 and 0.164 for tramadol and celecoxib, respectively. The selectivity was further evaluated by quantifying celecoxib and tramadol in the presence of potentially interfering drugs. The model demonstrated success in quantifying celecoxib and tramadol in laboratory-prepared tablets, producing metrics consistent with those reported in previously established spectrophotometric methods.

First derivative synchronous spectrofluorimetric method for the simultaneous determination of tramadol and celecoxib in their dosage forms and human plasma.

One of the most common features of many different clinical conditions is pain; hence, there is a crucial need for eliminating or reducing it to a tolerable level to retrieve physical, psychological and social functioning. A first derivative synchronous spectrofluorimetry technique is proposed for the simultaneous determination of celecoxib and tramadol HCl, a recent coformulation authorized for treating acute pain in adults. The method includes using synchronous spectrofluorimetry at ∆λ = 80 nm where tramadol HCl was determined using first derivative technique at λ = 230.2 nm, while celecoxib was determined at λ = 288.24 nm. The proposed method was successfully applied to their co-formulated dosage forms in addition to spiked human plasma and validated in agreement with the guidelines of the International Council for Harmonization of Technical Requirements for Pharmaceuticals for Human Use (ICH). The linear ranges were found to be 0.50-5.0 and 0.15-0.50, the limits of detection to be 0.088 and 0.011 and the limits of quantification to be 0.266 and 0.032 µg/ml for celecoxib and tramadol, respectively. Statistical analysis revealed no significant difference when compared with previously reported methods as evidenced by the values of the variance ratio F-test and Student t-test. The proposed method was successfully applied to commercial dosage forms and spiked human samples. Moreover, the greenness of the proposed method was investigated based on the analytical eco-scale approach, with the results showing an excellent green scale with a score of 95.

Simultaneous Determination of Docetaxel and Celecoxib in Porous Microparticles and Rat Plasma by Liquid-Liquid Extraction and HPLC with UV Detection: in vitro and in vivo Validation and Application.

PURPOSE: A simple, rapid, sensitive, and reliable HPLC method with UV detection was developed and validated for simultaneous quantitation of docetaxel and celecoxib and paclitaxel for dissolution characterization and pharmacokinetic studies. METHODS: The HPLC assay was performed isocratically on a reversed-phase C18 µ-Bondapack column using a mobile phase of acetonitrile:water (45:55, v/v) at a flow rate of 1.2 mL/min, and the analytes were detected at 230 nm. Paclitaxel was used as an internal standard for analysis of plasma samples following simple liquid-liquid extraction with n-hexane:isoamyl alcohol (97:3). The method was validated for specificity, linearity, sensitivity, precision, accuracy, robustness, and in vitro-in vivo application. RESULTS: The retention times for docetaxel, paclitaxel, and celecoxib were 10.94, 12.4, and 16.81 min, respectively. The standard curves covering 0.1-1 µg/mL and 0.05-4 µg/mL were linear using dissolution medium and rat plasma, respectively. The limit of quantitation of the method was 50 ng/mL using 100 µL of rat plasma sample and injection of 50 µL of the residue. Within- and between-day precision and accuracy did not exceed 16.86% and 12.10%, respectively. This validated method was successfully used to quantify docetaxel and celecoxib simultaneously in the release study of docetaxel- celecoxib -loaded porous microparticles and pharmacokinetics studies. The methods were found to be simple, specific, precise, accurate, and reproducible. In this study, paclitaxel was used as the internal standard while dexamethasone, flutamide, and budesonide proved suitable alternative as an internal standard. CONCLUSION: Since docetaxel and celecoxib could be co-administered for the treatment of a wide range of cancers such as non-small cell lung carcinoma, the developed method is particularly advantageous for routine therapeutic drug monitoring and pharmacokinetic studies of these drugs.

Role of solvent in differential phase behavior of celecoxib during spray drying.

Spray drying is an industrially viable technique that can be used for modulation of the physical form of Active Pharmaceutical Ingredients (API), which is governed by inherent crystallization tendency and processing parameters during spray drying. In the current study, we investigated the role of solvent in differential phase behavior of celecoxib, a poor crystallizer, during spray drying and unveiled the underlying mechanisms. 1% w/v solutions of celecoxib in three different compositions of methanol (M)-water (W) solvent system were spray dried using a laboratory spray dryer. The proportions were 0, 5 and 10% v/v of water in methanol (MW0, MW5, and MW10, respectively). Percentage crystallinity of the spray dried products were evaluated using modulated differential scanning calorimetry and was in the order MW10 > MW5 > MW0 (i.e. 18.52% > 8.13% > 0%). Solution-state and solid-state crystallization events responsible for the experimental observations were probed using microscopy, Raman spectroscopy, and non-isothermal crystallization studies. An intermediate amorphous phase was generated for the studied samples, which underwent crystallization under the influence of chamber temperature for MW5 and MW10. Additionally, liquid-liquid phase separation (LLPS) at very high level of supersaturation led to relatively higher crystallinity for MW10. Insights from this work provide the basis for understanding of probable phase behavior of poor crystallizers during spray drying.

A fast and green reversed-phase HPLC method with fluorescence detection for simultaneous determination of amlodipine and celecoxib in their newly approved fixed-dose combination tablets.

A fast, green, sensitive, and accurate analytical method using high-performance liquid chromatography couple with fluorescence detection was established and validated for the simultaneous determination of amlodipine besylate and celecoxib in their recently approved fixed-dose combination tablets (1:20). Separation of the two drugs was achieved on C18 reversed-phase column (Thermo ODS Hypersil, 4.6 × 250 mm, particle size 5 µm) using acetonitrile:potassium phosphate buffer (50 mM; pH 5.5, 60:40 v/v) as a mobile phase at 40°C, which eluted at a rate of 1 mL/min. Detection was carried out with excitation and emission wavelengths of 360 and 446 nm for amlodipine and 265 and 359 nm for celecoxib, respectively. The method was linear over a concentration range of 0.05-2 and 0.05-10 µg/mL and limit of detection reached to 0.017 and 0.0167 µg/mL for amlodipine and celecoxib, respectively. The developed method was successfully applied to assess the cited drugs in their newly FDA approved fixed-dose combination tablet dosage form. Furthermore, the method was found to be sensitive and eco-friendly green alternative to the reported methods as it was evaluated according to the green analytical procedure index tool guidelines and analytical Eco-Scale.

Dimethyldioctadecylanimonium bentonite immobilized magnetic chitosan nanoparticles as an efficient adsorbent for vortex-assisted magnetic dispersive micro-solid-phase extraction of celecoxib from human breast milk, plasma and urine samples.

A polymer/layered silicate composite based on dimethyldioctadecylanimonium bentonite/chitosan magnetic nanoparticles was synthesized and characterized by field emission transmission electron microscopy, X-ray diffraction and Fourier transform infrared spectrometry. The prepared nanocomposite was used to isolate and preconcentrate celecoxib from human breast milk, urine and plasma samples. In this method, dimethyldioctadecylanimonium bentonite increases the accessibility of binding sites and adsorption capacity by high microporosity and large surface area, that has been realized for the first time in a magnetic chitosan nanoparticle support. A fractional factorial design was utilized for screening the experimental parameters. The effective parameters were then optimized by Box-Behnken design. Under the optimized conditions, the developed method exhibited wide linear ranges of 5-500 µg L-1 for plasma and urine and 10-500 µg L-1 for breast milk samples with satisfactory recoveries in the range of 96.7-99.0%. Limit of detection and quantification of celecoxib were in the ranges 0.3-3.2 and 0.99-10.56, respectively. The enrichment factors were obtained in the ranges 64.5-66.0, while precisions were <3.7%.

Liquid chromatographic method for simultaneous determination of alprazolam with NSAIDs in bulk drug, pharmaceutical formulation and human serum.

High performance liquid chromatography with UV/vis detection was optimized and validated for simultaneous quantification of alprazolam with celecoxib and diclofenac sodium in pharmaceutical formulation and human serum. Chromatographic separation was achieved at detection wavelength of 230 nm on Shimadzu Shim-pack CLC-ODS (M) 25M column employing 80:20 (v/v) methanol: water (pH 3.5) as mobile phase with elution rate 1.0mL min-1. Analytes were quantified in the ranges 0.2-15, 0.3-20 and 0.6-40 µg mL-1 with detection limits 19.76, 17.29 and 11.83ng mL-1 respectively. Recoveries were in the range 98.15-101.15, 99.24-99.90 and 98.87-101.19% in pharmaceutical formulation and 98.05-101.01, 98.72-99.49 and 98.25-99.47% in human serum respectively and precision ranged from 0.19-1.84%. The analytes were successfully detected without any observable interference commonly present in pharmaceutical formulation and human serum demonstrating applicability of method.

Development of a Unified Reversed-Phase HPLC Method for Efficient Determination of EP and USP Process-Related Impurities in Celecoxib Using Analytical Quality by Design Principles.

This article presents the development of a reversed-phase (RP) high-performance liquid chromatographic (HPLC) method for determination of process-related impurities in a celecoxib drug substance following Analytical Quality by Design (AQbD) principles. The method from European Pharmacopeia (EP) for celecoxib drug substance does not sufficiently separate celecoxib from its EP impurity B because the system suitability criterion is not achieved (resolution NLT 1.8). The same issue was observed with the proposed method from United States Pharmacopeia (USP) for celecoxib capsules, where EP impurity A elutes under the main peak. A new HPLC method was developed that eliminates the disadvantages of the two pharmacopeial methods and is capable of efficiently separating and determining all seven impurities listed in EP and the proposed USP monographs. The development of a new HPLC method started with method scouting, in which various C18 and phenyl stationary phases were tested. Improved selectivity was obtained only with a chiral stationary phase. An immobilized Chiralpak IA-3 column used in RP mode turned out to be the most appropriate for method optimization. The ratio of acetonitrile in the mobile phase, flow rate, and column temperature were recognized as critical method parameters (CMPs) and were further investigated using a central composite face response-surface design. A multiple linear regression (MLR) method was applied to fit the mathematical models on the experimental data to determine factor-response relationships. The models created show adequate fit and good prediction abilities. The Monte Carlo simulation method was used to establish the design space. The method developed was verified in terms of precision, sensitivity, accuracy, and linearity, and the results showed that the new method is suitable for determination of seven process-related impurities of celecoxib.

Development and validation of a colorimetric method for the quantitative analysis of thioamide derivatives.

Thioamides (Thm) have diverse biological activities. This work presents the development and validation of simple, rapid and accurate spectrophotometric method for the analysis of Thm derivatives in pure form and in plasma. This spectrophotometric method has not been used before for determination of Thm. A review of the literature revealed that the monitoring of S- group assay is based on the reaction with DTNB according to the Ellman method to form a yellow complex which absorbs at 412 nm. To assay the thioamides according to this method it is necessary to make the basic medium have S- to react with the DTNB. Experimental conditions affecting the color development were studied and optimized. The proposed spectrophotometric procedures were effectively validated with respect to linearity, ranges, precision, accuracy, specificity, robustness, detection and quantification limits. Calibration curves of the formed colored product with DTNB showed good linear relationships over the concentration ranges (0, 50, 100, 500, 1000, 1500 mg/L). The proposed method was successfully applied to the assay of Thm monitoring with good accuracy. The principal advantages of the proposed method were rapidity and suitability for the routine quality control assay of the drug alone and in monitoring form without interference.

Celecoxib is a substrate of CYP2D6: Impact on celecoxib metabolism in individuals with CYP2C9*3 variants.

Celecoxib was characterized as a substrate of human cytochrome P450 (CYP) 2D6 in vitro. In recombinant CYP2D6, celecoxib hydroxylation showed atypical substrate inhibition kinetics with apparent Km, Ki, and Vmax of 67.2 µM, 12.6 µM, and 1.33 µM/min, respectively. In human liver microsomes (HLMs), a concentration-dependent inhibition of celecoxib hydroxylation by quinidine was observed after CYP2C9 and CYP3A4 were inhibited. In individual HLMs with variable CYP2D6 activities, a significant correlation was observed between celecoxib hydroxylation and CYP2D6-selective dextromethorphan O-demethylation when CYP2C9 and CYP3A4 activities were suppressed (r = 0.97, P < 0.0001). Molecular modeling showed two predominant docking modes of celecoxib with CYP2D6, resulting in either a substrate or an inhibitor. A second allosteric binding antechamber, which stabilized the inhibition mode, was revealed. Modeling results were consistent with the observed substrate inhibition kinetics. Using HLMs from individual donors, the relative contribution of CYP2D6 to celecoxib metabolism was found to be highly variable and dependent on CYP2C9 genotypes, ranging from no contribution in extensive metabolizers with CYP2C9*1*1 genotype to approximately 30% in slow metabolizers with allelic variants CYP2C9*1*3 and CYP2C9*3*3. These results demonstrate that celecoxib may become a potential victim of CYP2D6-associated drug-drug interactions, particularly in individuals with reduced CYP2C9 activity.

Adsorption of Celecoxib on B12N12 fullerene: Spectroscopic and DFT/TD-DFT study.

In this study, we evaluated the effect of the Celecoxib (CXB) adsorption on the electronic and optical properties of B12N12 fullerene by using density functional theory (DFT) and time-dependent density functional theory (TD-DFT) calculations with the M06-2X functional and the 6-311+G** basis set. The calculated adsorption energies of CXB with the B12N12 fullerene was evaluated at T = 298.15 K in the vacuum and solvent (water) environments with the M06-2X functional. UV absorption and IR spectra were calculated and studied in order to identify the most important changes happening as a consequence of interactions between CXB and B12N12 fullerene. The results revealed that the adsorption of the CXB molecule from its NH2 head on the B12N12 is more favorable than those of the SO2 and NH groups in the gas and solvent environments. It is anticipated that the applied B12N12 fullerene could be suitable as a biomedical carrier for the delivery of CXB drug.

Silver-choline chloride modified graphene oxide: Novel nano-bioelectrochemical sensor for celecoxib detection and CCD-RSM model.

In this study, silver nanoparticles modified choline chloride functionalized graphene oxide (AgNPs-ChCl-GO) was synthesized using sonochemical method and utilized as a bioelectrochemical sensor for detection of celecoxib (CEL). The characterization studies were ultimately performed in order to acheive a more complete understanding of the morphological and structural features of the AgNPs-ChCl-GO using different techniques including FT-IR, AFM, FE-SEM, EDX, and XRD. AgNPs-ChCl-GO demonstrated a significant improvement in the reduction activity of CEL due to the enhancement in the current response compared to the bare carbon paste electrode (CPE). The optimum experimental conditions, were optimized using central composite design (CCD) methodology. The differential pulse voltammetry (DPVs) showed an expanded linear dynamic ranges of 9.6 × 10-9-7.4 × 10-7 M for celecoxib in Britton-Robinson buffer in pH 5.0 with. LOD (S/N = 3) and LOQ (S/N = 10) were obtained 2.51 × 10-9 M and 6.58 × 10-9 M respectively. AgNPs-ChCl-GO-carbon paste electrode exhibited suitable properties and high accuracy determination of celecoxib in the human plasma sample.

Design, synthesis, biological evaluation, and nitric-oxide release studies of a novel series of celecoxib prodrugs possessing a nitric-oxide donor moiety

A new group of hybrid nitric oxide-releasing anti-inflammatory drugs (NONO-coxibs), in which an O 2-acetoxymethyl-1-(N-ethyl-N-methylamino)diazen-1-ium-1,2-diolate NO-donor moiety is attached directly to the carboxylic acid group of 1-(4-aminosulfonylphenyl)-5-aryl-1H-pyrazol-3-carboxylic acids (6a-c), were synthesized. A low amount of NO was released from the diazen-1-ium-1,2-diolate compounds 6a-c upon incubation with phosphate buffer saline (PBS) at pH 7.4 (range: pH 7.97-8.51), whereas, the percentage of NO released was significantly higher (84.5%-85.05% of the theoretical maximal release of two molecules of NO/molecule of the parent hybrid ester prodrug) when the diazen-1-ium-1,2-diolate ester prodrugs were incubated in the presence of rat serum. These incubation studies demonstrated that both NO and the anti-inflammatory 1-(4-aminosulfonylphenyl)-5-(4-H, 4-F or 4-Me-phenyl)-1H-pyrazol-3-carboxylic acid (4a-c) would be released from the parent NONO-coxib upon in vivo cleavage by non-specific serum esterases. The parent compounds 4a-c displayed good anti-inflammatory effects (ID50=81.4-112.4 mg/kg p.o.) between those exhibited by the reference drugs, aspirin (ID50=114.3 mg/kg p.o.) and celecoxib (ID50=12.6 mg/kg p.o.). Hybrid ester anti-inflammatory/NO-donor prodrugs (NONO-coxibs) offer a potential drug-design concept directed toward the development of anti-inflammatory drugs that are lacking adverse ulcerogenic and/or cardiovascular effects.

Development and validation of a LC-FL method for the simultaneous determination of doxorubicin and celecoxib in nanoparticulate fixed dose combination (NanoFDC).

An isocratic reversed phase HPLC method for the simultaneous determination of doxorubicine (DOX) and celecoxib (CXB) out of a nanoparticulate fixed dose combination (NanoFDC) was developed and validated. Linearity of the results was demonstrated from 1-11 µg/mL for both components. Lower limits of detection were determined as 7 ng/mL for DOX and 13 ng/mL for CXB. Total run time was approximately 15 min.

Grafting of allylimidazole and n-vinylcaprolactam as a thermosensitive polymer onto magnetic nano-particles for the extraction and determination of celecoxib in biological samples.

In this research, a novel method is reported for the surface grafting of n-vinylcaprolactam as a thermosensitive agent and allylimidazole with affinity toward celecoxib onto magnetic nano-particles. The grafted nano-particles were characterized by Fourier transform infrared spectroscopy, elemental analysis, and thermogravimetric analysis. The surface morphology was studied using Scanning Electron Microscopy. The resulting grafted nano-particles were used for the determination of trace celecoxib in biological human fluids and pharmaceutical samples. The profile of celecoxib uptake by the modified magnetic nano-particles indicated good accessibility of the active sites in the grafted copolymer. It was found that the adsorption behavior could be fitted by the Langmuir adsorption isotherm model. Solid phase extraction for biological fluids such as urine and serum were investigated. In this study, urine extraction recovery of more than 95% was obtained.

Stability indicating method development and validation for simultaneous estimation of atorvastatin calcium and celecoxib in bulk and niosomal formulation by RP-HPLC

The present work describes development and validation of a specific, sensitive, precise and stability-indicating high-performance liquid chromatographic method of analysis of atorvastatin calcium and celecoxib, both as a bulk drug and in niosomal formulation. The analysis has been performed by using Cosmosil-C18 column (4.6 mm´250 mm, 5 m) at 25 °C using acetonitrile: ammonium acetate buffer pH 5.0: methanol (50:25:25 v/v/v) as mobile phase. The detection was carried out at 277nm with a flow rate of 1.0mL/min. The retention times of Atorvastatin calcium and Celecoxib were 6.195 and 3.989min, respectively. The method was validated according to ICH guidelines, for specificity, precision, linearity, accuracy and robustness. Atorvastatin calcium and Celecoxib were subjected to stress conditions of hydrolysis, oxidation, photolysis and thermal degradation. The degradation was observed in oxidation and acid hydrolysis. The linearity for atorvastatin calcium and celecoxib were in the range of 100-500 µg/mL. The recovery study of atorvastatin and celecoxib were found to be in the range of 98.96 - 99.92% and 98.90-100%, respectively. The proposed method was validated and successfully applied to the estimation of Atorvastatin calcium and Celecoxib in combined in-house niosomal formulation.

O presente trabalho descreve o desenvolvimento e a validação de método de análise por cromatografia de alta eficiência específico, sensível, preciso e indicador de estabilidade de atorvastatina cálcica e celecoxibe, ambos como fármaco e como formulação niosômica. A análise foi realizada utilizando coluna Cosmosil-C18 (4,6 mm´250 mm, 5 m) a 25 °C, e acetonitrila: tampão acetato de amônio pH 5,0: metanol (50:25:25 v/v/v) como fase móvel. A detecção foi realizada a 277 nm, com fluxo de 1,0 mL/min. Os tempos de retenção de atorvastatina cálcica e de celecoxibe foram 6,195 e 3,989 min, respectivamente. O método foi validado de acordo com as regras da ICH para especificidade, precisão, exatidão e robustez. A atorvastatina cálcica e o celecoxibe foram submetidos a condições de estresse por hidrólise, oxidação, fotólise e degradação térmica. A degradação foi observada por oxidação e hidrólise ácida. Observou-se a linearidade da atorvastatina cálcica e do celecoxibe na faixa de 100-500 µg/mL. A recuperação da atorvastatina e do celecoxibe foi observada na faixa de 98,96-99,92% e 98,90-100%, respectivamente. O método proposto foi validado e aplicado com sucesso para a determinação de atorvastatina cálcica e celecoxibe em formulação niosômica caseira combinada.

Avaliação do potencial antiproliferativo do Dendrímero de Poliglicerol associado ao celecoxibe em linhagens celulares de carcinoma epidermoide de cabeça e pescoço / Evaluation of antiproliferative potential of Polyglycerol Dendrimer conjugated to Celecoxib in Head and Neck Squamous Cell Carcinoma cell lines

Diversos mecanismos celulares estão associados à patogênese do Carcinoma Epidermoide de Cabeça e Pescoço (CECP). Algumas dessas alterações envolvem proteínas pertencentes à via de sinalização do Akt, e o fator de transcrição NF-kB, o qual têm importante papel na fisiologia normal e no câncer. A proteína COX-2, descrita em processos inflamatórios, também participa da carcinogênese e está associada com a via de sinalização do Akt e com o NF-kB. Dendrímeros são uma forma única de nanotecnologia, surgindo como nanotransportadores com a capacidade de penetrar na célula tumoral liberando drogas quimioterápicas em seu interior. Os benefícios desta tecnologia são o aumento da eficicácia do princípio ativo utilizado e a redução dos seus efeitos secundários tóxicos. O Celecoxibe, antiinflamatório não esteroidal, inibidor seletivo da COX-2, tem se mostrado um importante agente anticarcinogênico, no entanto seu mecanismo de ação no CECP não é totalmente compreendido. Neste trabalho, um Dendrímero de Poliglicerol associado ao Celecoxibe (PGLD-celecoxibe) foi sintetizado e caracterizado por técnicas de espectroscopia ¹H-RMN, ¹³C-RMN, Maldi-Tof, TLC e DSC. Além disso, o conjugado foi testado in vitro em três linhagens celulares de CECP. O PGLD-Celecoxibe foi sintetizado com sucesso e promoveu a redução da dose capaz de inibir a proliferação celular, reduzindo o IC 50 do Celecoxibe de forma significativa em todas as linhagens celulares, se aproximando da dose sérica alcançada por este medicamento, resultado corroborado pelo Ensaio de Migração Celular. O mecanismo de morte celular observado foi a apoptose, associada a diminuição significativa da expressão de COX-2 ou por uma via alternativa independente. Alguns dos grupos tratados apresentaram alteração na expressão das proteínas pAkt e NF-kB.

Several cellular mechanisms are associated with the pathogenesis of Head and Neck Squamous Cell Carcinoma (HNSCC). Some of these alterations involve proteins in the Akt signaling pathway and the transcription factor NF-kB, which plays an important role in normal physiology and in cancer. COX-2 protein, described in inflammatory processes, and also involved in the carcinogenesis is associated with the Akt signaling pathway and the NF-kB. Dendrimers are a unique form of nanotechnology, emerging as nanocarriers with the ability to penetrate the tumor cell releasing chemotherapeutic. This technology increases the active substance efficiency and reduces its toxic side effects. Celecoxib, a nonsteroidal anti-inflammatory, selective inhibitor of COX-2 has been shown to be an important anticancer agent, but its action mechanism in HNSCC is not fully understood. A polyglycerol dendrimer linked to celecoxib (PGLD-Celecoxibe) was synthesized and characterized by NMR spectroscopy ¹H-NMR, ¹³C-NMR,TLD, DSC and Maldi-Tof techniques. In addition, in vitro assays were performed in three HNSCC cell lines The PGLD-Celecoxibe was successfully synthesized and provided a decrease in the dose able to inhibit cell proliferation reducing the IC 50 index of Celecoxib significantly in all cell lines, approaching to the serum dose achieved for this product, result supported by Wound Healing Assay. The cell death mechanism observed was apoptosis, which can be associated with significant reduction of expression of COX-2 also may be occurring by a COX-2 independent pathway. Some of the treated groups showed alterations in pAkt and NF-kB proteins expression.