Base de dados : MEDLINE Pesquisa : D02.241.223.100.050.400.200.555 [Categoria DeCS] Referências encontradas : 993 [refinar] Mostrando: 1 .. 10   no formato [Detalhado]

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[PMID]: 29095288 [Au] Autor: Kaosombatwattana U; Limsrivilai J; Pongpaibul A; Maneerattanaporn M; Charatcharoenwitthaya P [Ad] Endereço: aDivision of Gastroenterology, Department of Internal Medicine bDepartment of Pathology, Faculty of Medicine, Siriraj Hospital, Mahidol University, Bangkok, Thailand. [Ti] Título: Severe enteropathy with villous atrophy in prolonged mefenamic acid users - a currently under-recognized in previously well-recognized complication: Case report and review of literature. [So] Source: Medicine (Baltimore);96(44):e8445, 2017 Nov. [Is] ISSN: 1536-5964 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: RATIONALE: Mefenamic acid-induced enteropathy may be an under-recognized condition because few reported cases and no review of literature to comprehensively describe all reported cases exist. From inception until February 2017, a systematic literature search identified twenty original reports of cases of mefenamic acid-induced enteropathy. Additional five cases were identified at our hospital. All cases were included in the analyses. PATIENT CONCERNS: Most patients had been regularly taking therapeutic dosages of mefenamic acid for at least three months before symptoms developed. All patients presented with chronic diarrhea with significant weight loss. Approximately one-third of the cases had some degree of anemia and hypoalbuminemia. DIAGNOSES: Endoscopic findings could range from very mild abnormalities, such as mild atrophic mucosa, to marked abnormalities, such as blunted villi with scalloping appearance in the small intestine and inflamed mucosa with a few superficial ulcers in the ileum and colon. Pathological findings included flattened small intestinal villi and mixed inflammatory infiltrates including eosinophils in lamina propria. INTERVENTION: After identifying history of prolong mefenamic acid exposure, all patients were prescribed to stop this medication. Nutritional support and substitutional treatment for mefenamic acid were provided as well. OUTCOMES: All symptoms responded dramatically to drug withdrawal. Some patients could change to use other nonsteroidal anti-inflammatory drugs (NSAIDs) without symptoms reoccurring. LESSONS: Unlike other traditional NSAIDs, mefenamic acid could induce intestinal villous atrophy. An adequate drug history is crucial to identifying the condition. Protracted diarrhea occurring during treatment should be the indication to cease the medicine promptly. [Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/efeitos adversos Diarreia/induzido quimicamente Enteropatias/induzido quimicamente Efeitos Adversos de Longa Duração/induzido quimicamente Ácido Mefenâmico/efeitos adversos [Mh] Termos MeSH secundário: Adulto Idoso Anti-Inflamatórios não Esteroides/administração & dosagem Artralgia/tratamento farmacológico Feminino Seres Humanos Ácido Mefenâmico/administração & dosagem Meia-Idade Transtornos de Enxaqueca/tratamento farmacológico Fatores de Tempo [Pt] Tipo de publicação: CASE REPORTS; JOURNAL ARTICLE; REVIEW [Nm] Nome de substância: 0 (Anti-Inflammatory Agents, Non-Steroidal); 367589PJ2C (Mefenamic Acid) [Em] Mês de entrada: 1711 [Cu] Atualização por classe: 171113 [Lr] Data última revisão: 171113 [Sb] Subgrupo de revista: AIM; IM [Da] Data de entrada para processamento: 171103 [St] Status: MEDLINE [do] DOI: 10.1097/MD.0000000000008445

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[PMID]: 28759638 [Au] Autor: Alshehri S; Shakeel F; Ibrahim M; Elzayat E; Altamimi M; Shazly G; Mohsin K; Alkholief M; Alsulays B; Alshetaili A; Alshahrani A; Almalki B; Alanazi F [Ad] Endereço: Department of Pharmaceutics, College of Pharmacy, King Saud University, Riyadh, Saudi Arabia. [Ti] Título: Influence of the microwave technology on solid dispersions of mefenamic acid and flufenamic acid. [So] Source: PLoS One;12(7):e0182011, 2017. [Is] ISSN: 1932-6203 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: The present studies were undertaken to develop solvent-free solid dispersions (SDs) for poorly soluble anti-inflammatory drugs mefenamic acid (MA) and flufenamic acid (FFA) in order to enhance their in vitro dissolution rate and in vivo anti-inflammatory effects. The SDs of MA and FFA were prepared using microwaves irradiation (MW) technique. Different carriers such as Pluronic F127® (PL), Eudragit EPO® (EPO), polyethylene glycol 4000 (PEG 4000) and Gelucire 50/13 (GLU) were used for the preparation of SDs. Prepared MW irradiated SDs were characterized physicochemically using differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), Fourier transform infra-red (FT-IR) spectroscopy, powder X-ray diffraction (PXRD) and scanning electron microscopy (SEM). The physicochemical characteristics and drug release profile of SDs were compared with pure drugs. The results of DSC, TGA, FT-IR, PXRD and SEM showed that SDs were successfully prepared. In vitro dissolution rate of MA and FFA was remarkably enhanced by SDs in comparison with pure MA and FFA. The SDs of MA and FFA prepared using PEG 400 showed higher drug release profile in comparison with those prepared using PL, EPO or GLU. The dissolution efficiency for MA-PEG SD and FFA-PEG SD was obtained as 61.40 and 59.18%, respectively. Optimized SDs were also evaluated for in vivo anti-inflammatory effects in male Wistar rats. The results showed significant % inhibition by MA-PEG (87.74% after 4 h) and FFA-PEG SDs (81.76% after 4 h) in comparison with pure MA (68.09% after 4 h) and pure FFA (55.27% after 4 h) (P<0.05). These results suggested that MW irradiated SDs of MA and FFA could be successfully used for the enhancement of in vitro dissolution rate and in vivo therapeutic efficacy of both drugs. [Mh] Termos MeSH primário: Anti-Inflamatórios/efeitos da radiação Ácido Flufenâmico/efeitos da radiação Ácido Mefenâmico/efeitos da radiação Micro-Ondas [Mh] Termos MeSH secundário: Anti-Inflamatórios/química Ácido Flufenâmico/química Ácido Mefenâmico/química Solubilidade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Anti-Inflammatory Agents); 367589PJ2C (Mefenamic Acid); 60GCX7Y6BH (Flufenamic Acid) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170928 [Lr] Data última revisão: 170928 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170801 [St] Status: MEDLINE [do] DOI: 10.1371/journal.pone.0182011

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[PMID]: 28398095 [Au] Autor: Wenzel T; Stillhart C; Kleinebudde P; Szepes A [Ad] Endereço: a Formulation Research and Development , F. Hoffmann-La Roche Ltd , Basel , Switzerland. [Ti] Título: Influence of drug load on dissolution behavior of tablets containing a poorly water-soluble drug: estimation of the percolation threshold. [So] Source: Drug Dev Ind Pharm;43(8):1265-1275, 2017 Aug. [Is] ISSN: 1520-5762 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Drug load plays an important role in the development of solid dosage forms, since it can significantly influence both processability and final product properties. The percolation threshold of the active pharmaceutical ingredient (API) corresponds to a critical concentration, above which an abrupt change in drug product characteristics can occur. The objective of this study was to identify the percolation threshold of a poorly water-soluble drug with regard to the dissolution behavior from immediate release tablets. The influence of the API particle size on the percolation threshold was also studied. Formulations with increasing drug loads were manufactured via roll compaction using constant process parameters and subsequent tableting. Drug dissolution was investigated in biorelevant medium. The percolation threshold was estimated via a model dependent and a model independent method based on the dissolution data. The intragranular concentration of mefenamic acid had a significant effect on granules and tablet characteristics, such as particle size distribution, compactibility and tablet disintegration. Increasing the intragranular drug concentration of the tablets resulted in lower dissolution rates. A percolation threshold of approximately 20% v/v could be determined for both particle sizes of the API above which an abrupt decrease of the dissolution rate occurred. However, the increasing drug load had a more pronounced effect on dissolution rate of tablets containing the micronized API, which can be attributed to the high agglomeration tendency of micronized substances during manufacturing steps, such as roll compaction and tableting. Both methods that were applied for the estimation of percolation threshold provided comparable values. [Mh] Termos MeSH primário: Composição de Medicamentos/métodos Excipientes/química Ácido Mefenâmico/farmacocinética Comprimidos Água/química [Mh] Termos MeSH secundário: Química Farmacêutica Liberação Controlada de Fármacos Cinética Ácido Mefenâmico/química Tamanho da Partícula Solubilidade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Excipients); 0 (Tablets); 059QF0KO0R (Water); 367589PJ2C (Mefenamic Acid) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170914 [Lr] Data última revisão: 170914 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170412 [St] Status: MEDLINE [do] DOI: 10.1080/03639045.2017.1313856

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[PMID]: 28259989 [Au] Autor: Shiiba M; Yamagami H; Yamamoto A; Minakawa Y; Okamoto A; Kasamatsu A; Sakamoto Y; Uzawa K; Takiguchi Y; Tanzawa H [Ad] Endereço: Department of Oral Science, Graduate School of Medicine, Chiba University, Chuo-ku, Chiba 260-8670, Japan. [Ti] Título: Mefenamic acid enhances anticancer drug sensitivity via inhibition of aldo-keto reductase 1C enzyme activity. [So] Source: Oncol Rep;37(4):2025-2032, 2017 Apr. [Is] ISSN: 1791-2431 [Cp] País de publicação: Greece [La] Idioma: eng [Ab] Resumo: Resistance to anticancer medications often leads to poor outcomes. The present study explored an effective approach for enhancing chemotherapy targeted against human cancer cells. Real-time quantitative real-time polymerase chain reaction (qRT-PCR) analysis revealed overexpression of members of aldo-keto reductase (AKR) 1C family, AKR1C1, AKR1C2, AKR1C3, and AKR1C4, in cisplatin, cis-diamminedichloroplatinum (II) (CDDP)-resistant human cancer cell lines, HeLa (cervical cancer cells) and Sa3 (oral squamous cell carcinoma cells). The genes were downregulated using small-interfering RNA (siRNA) transfection, and the sensitivity to CDDP or 5-fluorouracil (5-FU) was investigated. When the genes were knocked down, sensitivity to CDDP and 5-FU was restored. Furthermore, we found that administration of mefenamic acid, a widely used non-steroidal anti-inflammatory drug (NSAID) and a known inhibitor of AKR1Cs, enhanced sensitivity to CDDP and 5-FU. The present study suggests that AKR1C family is closely associated with drug resistance to CDDP and 5-FU, and mefenamic acid enhances their sensitivity through its inhibitory activity in drug-resistant human cancer cells. Thus, the use of mefenamic acid to control biological function of AKR1C may lead to effective clinical outcomes by overcoming anticancer drug resistance. [Mh] Termos MeSH primário: 20-Hidroxiesteroide Desidrogenases/biossíntese 3-Hidroxiesteroide Desidrogenases/biossíntese Hidroxiprostaglandina Desidrogenases/biossíntese Hidroxiesteroide Desidrogenases/biossíntese Ácido Mefenâmico/administração & dosagem Neoplasias/tratamento farmacológico [Mh] Termos MeSH secundário: 20-Hidroxiesteroide Desidrogenases/antagonistas & inibidores 20-Hidroxiesteroide Desidrogenases/genética 3-Hidroxiesteroide Desidrogenases/antagonistas & inibidores 3-Hidroxiesteroide Desidrogenases/genética Membro C3 da Família 1 de alfa-Ceto Redutase Cisplatino/administração & dosagem Resistência a Medicamentos Antineoplásicos/efeitos dos fármacos Fluoruracila/administração & dosagem Regulação Neoplásica da Expressão Gênica/efeitos dos fármacos Células HeLa Seres Humanos Hidroxiprostaglandina Desidrogenases/antagonistas & inibidores Hidroxiprostaglandina Desidrogenases/genética Hidroxiesteroide Desidrogenases/antagonistas & inibidores Hidroxiesteroide Desidrogenases/genética Neoplasias/genética Neoplasias/patologia Oxirredutases [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 367589PJ2C (Mefenamic Acid); EC 1.- (Oxidoreductases); EC 1.1.- (3-Hydroxysteroid Dehydrogenases); EC 1.1.- (Hydroxysteroid Dehydrogenases); EC 1.1.1.- (20-Hydroxysteroid Dehydrogenases); EC 1.1.1.- (3 alpha-beta, 20 beta-hydroxysteroid dehydrogenase); EC 1.1.1.- (Hydroxyprostaglandin Dehydrogenases); EC 1.1.1.357 (AKR1C2 protein, human); EC 1.1.1.357 (AKR1C3 protein, human); EC 1.1.1.357 (Aldo-Keto Reductase Family 1 Member C3); EC 1.3.1.20 (trans-1,2-dihydrobenzene-1,2-diol dehydrogenase); Q20Q21Q62J (Cisplatin); U3P01618RT (Fluorouracil) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 171116 [Lr] Data última revisão: 171116 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170306 [St] Status: MEDLINE [do] DOI: 10.3892/or.2017.5480

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[PMID]: 28259712 [Au] Autor: Savjani JK; Mulamkattil S; Variya B; Patel S [Ad] Endereço: Institute of Pharmacy, Nirma University, S.G.Highway, Ahmedabad, Gujarat 382481, India. Electronic address: Jignasasavjani@gmail.com. [Ti] Título: Molecular docking, synthesis and biological screening of mefenamic acid derivatives as anti-inflammatory agents. [So] Source: Eur J Pharmacol;801:28-34, 2017 Apr 15. [Is] ISSN: 1879-0712 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Drug induced gastrointestinal ulceration, renal side effects and hepatotoxicity are the main causes of numerous Non-Steroidal Anti-inflammatory Drugs (NSAIDs). Cyclooxygenase-2 (COX-2) inhibitors discovered to decrease the gastrointestinal issues, but unfortunately, most of them are associated with major cardiovascular adverse effects. Along these lines, various new strategies and frameworks were developed wherein basic alterations of the present medications were accounted for. The aim of the study was to prepare derivatives of mefenamic acid to evaluate anti-inflammatory activity with fewer adverse reactions. In this study, molecular docking investigations of outlined derivatives were done utilizing Protein Data Bank (PDB ID-4PH9). Synthesis of heterocyclic compounds was carried out utilizing Dicyclohexylcarbodiimide/4-Dimethylaminopyridine (DCC/DMAP) coupling. Acute toxicity prediction was performed using free online GUSAR (General Unrestricted Structure-Activity Relationships) software. The study indicated most of the compounds under safe category. In-vitro pharmacological assessment of heterocyclic compounds was done for COX-1 and COX-2 enzymes for the determination of selectivity. In vivo pharmacological screening for anti-inflammatory activity and ED value were determined utilizing carrageenan induced rat paw edema. Gastro intestinal safety study was carried out on selected compounds and found to be devoid of any gastric ulcer toxicity. Most of the compounds indicated high scores as compared to standard during molecular modelling, analysis and displayed interactions with active amino acids of a COX-2 enzyme. The pharmacological screening uncovered that compound substituted with p-bromophenyl indicated maximum potency. [Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/síntese química Anti-Inflamatórios não Esteroides/farmacologia Ácido Mefenâmico/síntese química Ácido Mefenâmico/farmacologia Simulação de Acoplamento Molecular [Mh] Termos MeSH secundário: Amidas/química Animais Anti-Inflamatórios não Esteroides/química Anti-Inflamatórios não Esteroides/metabolismo Técnicas de Química Sintética Ciclo-Oxigenase 1/química Ciclo-Oxigenase 1/metabolismo Ciclo-Oxigenase 2/química Ciclo-Oxigenase 2/metabolismo Avaliação Pré-Clínica de Medicamentos Ácido Mefenâmico/química Ácido Mefenâmico/metabolismo Conformação Proteica Ratos Ratos Wistar Relação Estrutura-Atividade [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Amides); 0 (Anti-Inflammatory Agents, Non-Steroidal); 367589PJ2C (Mefenamic Acid); EC 1.14.99.1 (Cyclooxygenase 1); EC 1.14.99.1 (Cyclooxygenase 2) [Em] Mês de entrada: 1704 [Cu] Atualização por classe: 170417 [Lr] Data última revisão: 170417 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170306 [St] Status: MEDLINE

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[PMID]: 28159976 [Au] Autor: Kim EC; Toyono T; Berlinicke CA; Zack DJ; Jurkunas U; Usui T; Jun AS [Ad] Endereço: Wilmer Eye Institute, Johns Hopkins Medical Institutions, Baltimore, Maryland, United States 2Department of Ophthalmology & Visual Science, Catholic University of Korea, Seoul, Korea. [Ti] Título: Screening and Characterization of Drugs That Protect Corneal Endothelial Cells Against Unfolded Protein Response and Oxidative Stress. [So] Source: Invest Ophthalmol Vis Sci;58(2):892-900, 2017 Feb 01. [Is] ISSN: 1552-5783 [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: Purpose: To screen for and characterize compounds that protect corneal endothelial cells against unfolded protein response (UPR) and oxidative stress. Methods: Bovine corneal endothelial cells (BCECs) were treated for 48 hours with 640 compounds from a Food and Drug Administration (FDA)-approved drug library and then challenged with thapsigargin or H2O2 to induce UPR or oxidative stress, respectively. Cell viability was measured using the CellTiter-Glo survival assay. Selected "hits" were subjected to further dose-response testing, and their ability to modulate expression of UPR and oxidative stress markers was assessed by RT-PCR, Western blot, and measurement of protein carbonyl and 8-hydroxydeoxyguanosine (8-OHdG) adducts in immortalized human corneal endothelial cells (iHCECs). Results: Forty-one drugs at 20 µM and 55 drugs at 100 µM increased survival of H2O2-challenged cells, and 8 drugs at 20 µM and 2 drugs at 100 µM increased survival of thapsigargin-challenged cells, compared with untreated control cells. Nicergoline, ergothioneine, nimesulide, oxotremorine, and mefenamic acid increased survival of both H2O2- and thapsigargin-challenged cells. Oxotremorine altered DNA damage inducible 3 (CHOP) gene expression, glucose-regulated protein 78 kDa (GRP78) and activating transcription factor 4 (ATF4) protein expression, and protein carbonyl and 8-OHdG levels. Mefenamic acid altered GRP78 protein expression and protein carbonyl and 8-OHdG levels. Conclusions: Oxotremorine and mefenamic acid are potential survival factors for corneal endothelial cells under UPR and oxidative stress. The described assay can be further expanded to screen additional drugs for potential therapeutic effect in corneal endothelial diseases such as Fuchs' endothelial corneal dystrophy. [Mh] Termos MeSH primário: Antioxidantes/farmacologia Células Endoteliais/efeitos dos fármacos Epitélio Posterior/efeitos dos fármacos Estresse Oxidativo/efeitos dos fármacos Resposta a Proteínas não Dobradas/efeitos dos fármacos [Mh] Termos MeSH secundário: Western Blotting Sobrevivência Celular/efeitos dos fármacos Inibidores de Ciclo-Oxigenase/farmacologia Desoxiguanosina/análogos & derivados Desoxiguanosina/metabolismo Relação Dose-Resposta a Droga Células Endoteliais/metabolismo Epitélio Posterior/citologia Epitélio Posterior/metabolismo Inibidores Enzimáticos/farmacologia Seres Humanos Peróxido de Hidrogênio/farmacologia Ácido Mefenâmico/farmacologia Agonistas Muscarínicos/farmacologia Oxotremorina/farmacologia Carbonilação Proteica/efeitos dos fármacos Reação em Cadeia da Polimerase Via Transcriptase Reversa Tapsigargina/farmacologia [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Antioxidants); 0 (Cyclooxygenase Inhibitors); 0 (Enzyme Inhibitors); 0 (Muscarinic Agonists); 367589PJ2C (Mefenamic Acid); 5RY0UWH1JL (Oxotremorine); 67526-95-8 (Thapsigargin); 88847-89-6 (8-oxo-7-hydrodeoxyguanosine); BBX060AN9V (Hydrogen Peroxide); G9481N71RO (Deoxyguanosine) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 171016 [Lr] Data última revisão: 171016 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170205 [St] Status: MEDLINE [do] DOI: 10.1167/iovs.16-20147

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[PMID]: 28091995 [Au] Autor: Velázquez YF; Nacheva PM [Ad] Endereço: National Autonomous University of Mexico, Campus IMTA, Paseo Cuauhnáhuac 8532, Progreso, 62550, Jiutepec, Morelos, Mexico. [Ti] Título: Biodegradability of fluoxetine, mefenamic acid, and metoprolol using different microbial consortiums. [So] Source: Environ Sci Pollut Res Int;24(7):6779-6793, 2017 Mar. [Is] ISSN: 1614-7499 [Cp] País de publicação: Germany [La] Idioma: eng [Ab] Resumo: The biodegradation of fluoxetine, mefenamic acid, and metoprolol using ammonium-nitrite-oxidizing consortium, nitrite-oxidizing consortium, and heterotrophic biomass was evaluated in batch tests applying different retention times. The ammonium-nitrite-oxidizing consortium presented the highest biodegradation percentages for mefenamic acid and metoprolol, of 85 and 64% respectively. This consortium was also capable to biodegrade 79% of fluoxetine. The heterotrophic consortium showed the highest ability to biodegrade fluoxetine reaching 85%, and it also had a high potential for biodegrading mefenamic acid and metoprolol, of 66 and 58% respectively. The nitrite-oxidizing consortium presented the lowest biodegradation of the three pharmaceuticals, of less than 48%. The determination of the selected pharmaceuticals in the dissolved phase and in the biomass indicated that biodegradation was the major removal mechanism of the three compounds. Based on the obtained results, the biodegradation kinetics was adjusted to pseudo-first-order for the three pharmaceuticals. The values of k for fluoxetine, mefenamic acid, and metoprolol determined with the three consortiums indicated that ammonium-nitrite-oxidizing and heterotrophic biomass allow a partial biodegradation of the compounds, while no substantial biodegradation can be expected using nitrite-oxidizing consortium. Metoprolol was the less biodegradable compound. The sorption of fluoxetine and mefenamic acid onto biomass had a significant contribution for their removal (6-14%). The lowest sorption coefficients were obtained for metoprolol indicating that the sorption onto biomass is poor (3-4%), and the contribution of this process to the global removal can be neglected. [Mh] Termos MeSH primário: Fluoxetina/análise Ácido Mefenâmico/análise Metoprolol/análise Consórcios Microbianos Poluentes Químicos da Água/análise [Mh] Termos MeSH secundário: Biodegradação Ambiental Reatores Biológicos Processos Heterotróficos Cinética Oxirredução Esgotos [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Sewage); 0 (Water Pollutants, Chemical); 01K63SUP8D (Fluoxetine); 367589PJ2C (Mefenamic Acid); GEB06NHM23 (Metoprolol) [Em] Mês de entrada: 1705 [Cu] Atualização por classe: 171104 [Lr] Data última revisão: 171104 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170117 [St] Status: MEDLINE [do] DOI: 10.1007/s11356-017-8413-y

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[PMID]: 27884714 [Au] Autor: Tierney T; Bodnár K; Rasmuson Å; Hudson S [Ad] Endereço: Synthesis and Solid State Pharmaceutical Centre, Department of Chemical Sciences, Bernal Institute, University of Limerick, Limerick, Ireland. Electronic address: Teresa.Tierney@ul.ie. [Ti] Título: Carrier particle design for stabilization and isolation of drug nanoparticles. [So] Source: Int J Pharm;518(1-2):111-118, 2017 Feb 25. [Is] ISSN: 1873-3476 [Cp] País de publicação: Netherlands [La] Idioma: eng [Ab] Resumo: Nanoparticles of poorly water-soluble drugs were prepared in suspension via antisolvent precipitation in order to improve their dissolution behaviour. Insoluble, surface-functionalized, micron-range, clay carrier particles were employed for the dual purpose of stabilizing the nanoparticles in suspended state, and facilitating their unhindered isolation to solid state; often a challenging step in nanoparticle production. The carrier particles, which were functionalized with an optimal level of cationic polymer (protamine), attracted negatively-charged nanoparticles to their surface as a uniform and segregated nanoparticle layer, at drug loadings up to 9% w/w. By using carrier particles to stabilise the nanoparticles on their surface, the traditionally used solubilised nanosuspension stabilisers could be eliminated, thus avoiding time-consuming stabiliser screening tests. The carrier particle system facilitated stabilisation of nanoparticles in suspension, isolation of nanoparticles to the solid state via filtration, and preservation of fast nanoparticle-induced dissolution rates of the dried nanoparticle-carrier composites, indicating preservation of their high surface area during drying. The process was validated with two poorly water-soluble BCS Class II drugs, fenofibrate and mefenamic acid, both of which demonstrated negative surface charge in aqueous suspension. [Mh] Termos MeSH primário: Portadores de Fármacos/química Nanopartículas/química [Mh] Termos MeSH secundário: Bentonita/química Composição de Medicamentos Estabilidade de Medicamentos Fenofibrato/química Ácido Mefenâmico/química Tamanho da Partícula Difração de Pó Protaminas/química Solubilidade Difração de Raios X [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Drug Carriers); 0 (Protamines); 1302-78-9 (Bentonite); 367589PJ2C (Mefenamic Acid); U202363UOS (Fenofibrate) [Em] Mês de entrada: 1706 [Cu] Atualização por classe: 170607 [Lr] Data última revisão: 170607 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 161126 [St] Status: MEDLINE

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[PMID]: 27681773 [Au] Autor: Ibrahim F; Sharaf El-Din MK; El-Deen AK; Shimizu K [Ad] Endereço: Department of Pharmaceutical Analytical Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt. [Ti] Título: Micellar HPLC Method for Simultaneous Determination of Ethamsylate and Mefenamic Acid in Presence of Their Main Impurities and Degradation Products. [So] Source: J Chromatogr Sci;55(1):23-29, 2017 01. [Is] ISSN: 1945-239X [Cp] País de publicação: United States [La] Idioma: eng [Ab] Resumo: An eco-friendly sensitive, rapid and less hazardous micellar liquid chromatographic method was developed and validated for the simultaneous analysis of ethamsylate (ETM) and mefenamic acid (MFA) in the presence of hydroquinone (HQ) and 2,3-dimethylaniline (DMA) the main impurities of ETM and MFA, respectively. Good chromatographic separation was attained using Eclipse XDB-C8 column (150 mm × 4.6 mm, 5 µm particle size) adopting UV detection at 300 nm with micellar mobile phase consisting of 0.12 M sodium dodecyl sulfate, 0.3% triethylamine and 15% 2-propanol in 0.02 M orthophosphoric acid (pH 7.0) at 1.0 mL/min. The analytes were well resolved in <6.0 min, ETM (t = 1.55 min), HQ (t = 1.95 min), MFA (t = 4.55 min) and DMA (t = 5.80 min). Different validation parameters were examined as recommended by international conference on harmonization (ICH) guidelines. The method was linear over the concentration ranges of 0.5-18.0, 0.5-20.0, 0.01-0.5 and 0.02-0.2 µg/mL with limits of detection of 0.118, 0.159, 0.005 and 0.005 µg/mL and limits of quantification of 0.358, 0.482, 0.014 and 0.015 µg/mL for ETM, MFA, HQ and DMA, respectively. The suggested method was successfully applied for the determination of the two drugs in their bulk powder, laboratory-prepared mixtures, single-ingredient and co-formulated tablets. The obtained results were in accordance with those of the comparison method. The method can also detect trace amounts of HQ and DMA as the main impurities of ETM and MFA, respectively, within the BP limit (0.1%) for both impurities. Furthermore, it is a stability-indicating one for the determination of ETM in its pure form, single-component tablet and co-formulated tablets with other drugs. [Mh] Termos MeSH primário: Cromatografia Líquida de Alta Pressão/métodos Etamsilato/análise Ácido Mefenâmico/análise Micelas [Mh] Termos MeSH secundário: Etamsilato/química Limite de Detecção Modelos Lineares Ácido Mefenâmico/química Reprodutibilidade dos Testes [Pt] Tipo de publicação: JOURNAL ARTICLE [Nm] Nome de substância: 0 (Micelles); 24YL531VOH (Ethamsylate); 367589PJ2C (Mefenamic Acid) [Em] Mês de entrada: 1709 [Cu] Atualização por classe: 170921 [Lr] Data última revisão: 170921 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 160930 [St] Status: MEDLINE

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MEDLINE

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[PMID]: 28370591 [Au] Autor: Aguiar GC; Queiroz-Junior CM; Sitta GL; Amaral FA; Teixeira MM; Caliari MV; Ferreira AJ [Ad] Endereço: Department of Morphology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Belo Horizonte, Brazil. [Ti] Título: Mefenamic acid decreases inflammation but not joint lesions in experimental osteoarthritis. [So] Source: Int J Exp Pathol;97(6):438-446, 2016 12. [Is] ISSN: 1365-2613 [Cp] País de publicação: England [La] Idioma: eng [Ab] Resumo: Mefenamic acid is a non-steroidal anti-inflammatory drug able to control the symptoms of osteoarthritis (OA), but its effects on protection of cartilage and bone are still unclear. This study aimed to investigate whether the control of inflammation by mefenamic acid translates into decreased joint lesions in experimental OA in rats. OA was induced by injecting 1 mg of monosodium iodoacetate (MIA) into the joints of rats. The animals were treated with mefenamic acid (50 mg/kg, daily, oral gavage) either pre-MIA injection (preventive) or post-MIA injection (therapeutic). Joint swelling and hyperalgesia were evaluated at baseline and 1, 3, 14 and 28 days after induction of OA. Intra-articular lavage and kinetics of cell migration into the synovium were measured 3 and 28 days after OA induction. Histopathological analysis, Osteoarthritis Research Society International (OARSI) score, total synovium cells count, cartilage area and levels of proteoglycans in joints were also evaluated. Mefenamic acid prevented joint oedema and hyperalgesia induced by MIA in the acute phase (3 days) of the disease. In the chronic phase (28 days), preventive and therapeutic regimens decreased the number of mononuclear cells in the joint cavity. In contrast, thickening of the synovium, bone resorption, loss of cartilage and levels of proteoglycans were unaffected by mefenamic acid when it was administered either preventively or therapeutically. Thus, mefenamic acid had anti-inflammatory effects but did not reduce the progression of OA lesions, thereby indicating that it is only effective for symptomatic control of OA. [Mh] Termos MeSH primário: Anti-Inflamatórios não Esteroides/uso terapêutico Inflamação/tratamento farmacológico Ácido Mefenâmico/uso terapêutico Osteoartrite/tratamento farmacológico [Mh] Termos MeSH secundário: Animais Anti-Inflamatórios não Esteroides/farmacologia Osso e Ossos/efeitos dos fármacos Osso e Ossos/patologia Cartilagem/efeitos dos fármacos Cartilagem/patologia Modelos Animais de Doenças Inflamação/patologia Articulações/efeitos dos fármacos Articulações/patologia Masculino Ácido Mefenâmico/farmacologia Osteoartrite/patologia Ratos [Pt] Tipo de publicação: JOURNAL ARTICLE; RESEARCH SUPPORT, NON-U.S. GOV'T [Nm] Nome de substância: 0 (Anti-Inflammatory Agents, Non-Steroidal); 367589PJ2C (Mefenamic Acid) [Em] Mês de entrada: 1707 [Cu] Atualização por classe: 171119 [Lr] Data última revisão: 171119 [Sb] Subgrupo de revista: IM [Da] Data de entrada para processamento: 170404 [St] Status: MEDLINE [do] DOI: 10.1111/iep.12216

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