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1.
J Chromatogr A ; 1621: 461085, 2020 Jun 21.
Artigo em Inglês | MEDLINE | ID: mdl-32376018

RESUMO

Two analytical methodologies based on the combined use of hydroxypropyl-ß-cyclodextrin and two different amino acid-based chiral ionic liquids (tetrabutylammonium-L-lysine or tetrabutylammonium-L-glutamic acid) in electrokinetic chromatography were developed in this work to perform the enantioselective determination of econazole and sulconazole in pharmaceutical formulations. The influence of different experimental variables such as buffer concentration, applied voltage, nature and concentration of the ionic liquid, temperature and injection time, on the enantiomeric separation was investigated. The combination of hydroxypropyl-ß-cyclodextrin and tetrabutylammonium-L-lysine under the optimized conditions enabled to achieve the enantiomeric determination of both drugs with high enantiomeric resolution (3.5 for econazole and 2.4 for sulconazole). The analytical characteristics of the developed methodologies were evaluated in terms of linearity, precision, LOD, LOQ and recovery showing good performance for the determination of both drugs which were successfully quantitated in pharmaceutical formulations. This work reports the first analytical methodology enabling the enantiomeric determination of sulconazole in pharmaceutical formulations.


Assuntos
2-Hidroxipropil-beta-Ciclodextrina/química , Cromatografia Capilar Eletrocinética Micelar/métodos , Econazol/análise , Ácido Glutâmico/química , Imidazóis/análise , Líquidos Iônicos/química , Lisina/química , Compostos de Amônio Quaternário , Estereoisomerismo , Temperatura , Fatores de Tempo
2.
Mikrochim Acta ; 187(1): 55, 2019 12 17.
Artigo em Inglês | MEDLINE | ID: mdl-31848716

RESUMO

An electrochromatographic capillary was modified with graphene oxide (GO), and the coating was characterized by scanning electron microscopy, energy dispersive X-ray spectrometry, and Fourier transform infrared spectra. By utilizing maltodextrin (MD) as the chiral selector, the basic chiral drugs nefopam (NEF), amlodipine (AML), citalopram hydrobromide (CIT), econazole (ECO), ketoconazole (KET) and cetirizine hydrochloride (CET) can be enantiomerically separated on this CEC. Compared with an uncoated silica capillary, the resolutions are markedly improved (AML: 0.32 → 1.45; ECO: 0.55 → 1.89; KET: 0.88 → 4.77; CET: 0.81 → 2.46; NEF: 1.46 → 2.83; CIT: 1.77 → 4.38). Molecular modeling was applied to demonstrate the mechanism of enantioseparation, which showed a good agreement with the experimental results. Graphical abstractSchematic representation of the preparation of graphene oxide-modified capillary (GO@capillary) for enantioseparation of drug enantiomers. The monolayered GO was used as the coating of the GO@capillary. Then the capillary was applied to construct capillary electrochromatography system with maltodextrin for separation of basic chiral drugs.


Assuntos
Grafite/química , Polissacarídeos/química , Anlodipino/química , Anlodipino/isolamento & purificação , Eletrocromatografia Capilar , Cetirizina/química , Cetirizina/isolamento & purificação , Citalopram/química , Citalopram/isolamento & purificação , Econazol/química , Econazol/isolamento & purificação , Cetoconazol/química , Cetoconazol/isolamento & purificação , Simulação de Acoplamento Molecular , Estrutura Molecular , Nefopam/química , Nefopam/isolamento & purificação , Tamanho da Partícula , Propriedades de Superfície
3.
Acta Dermatovenerol Croat ; 27(3): 137-141, 2019 Sep.
Artigo em Inglês | MEDLINE | ID: mdl-31542055

RESUMO

Pemphigus vulgaris is an autoimmune disease that mostly affects the mucosa and oral cavity. Candida species can invade the mucosal lesions of these patients and cause diseases. The aim of this study was to identify the fungal agents isolated from mucosal lesions and evaluate antifungal activity profile against the isolates. A total of 25 patients with pemphigus vulgaris with active oral lesions and 25 healthy people serving as a control group were included in this study. Identification of the fungal isolates was performed based on conventional methods and DNA sequence analysis of the internal transcribed spacer (ITS) rDNA gene region. The sequence results were deposited in the NCBI database using the Basic Local Alignment Search Tool. Antifungal activity of fluconazole, itraconazole, ketoconazole, posaconazole, econazole, and amphotericin B against the isolates were evaluated based on the CLSI M-44 A protocol. Oral candidiasis was detected in 20% of the patients. Candida species isolated from oral lesions of patients with pemphigus were identified as Candida albicans 22/25, Candida glabrata 2/25, and Candida dubliniensis 1/25. All of the isolates were sensitive to amphotericin and econazole, 96% to fluconazole and posaconazole, and 92% to ketoconazole and itraconazole. One patient showed a profile resistant to fluconazole, posaconazole, and ketoconazole, simultaneously. Ninety six percent of control group isolates were sensitive to six antifungals. Candida albicans was the most prevalent species isolated from oral lesions of patients with pemphigus vulgaris and the control group. Amphotericin B and econazole were the most effective antifungals against the isolates.


Assuntos
Antifúngicos/farmacologia , Candida/efeitos dos fármacos , Candida/isolamento & purificação , Candidíase Bucal/microbiologia , Pênfigo/microbiologia , Adulto , Anfotericina B/farmacologia , Candidíase Bucal/tratamento farmacológico , Candidíase Bucal/patologia , Testes de Sensibilidade a Antimicrobianos por Disco-Difusão , Econazol/farmacologia , Feminino , Fluconazol/farmacologia , Humanos , Itraconazol/farmacologia , Cetoconazol/farmacologia , Masculino , Pênfigo/tratamento farmacológico , Pênfigo/patologia , Triazóis/farmacologia
4.
Int J Mol Sci ; 20(15)2019 Jul 27.
Artigo em Inglês | MEDLINE | ID: mdl-31357647

RESUMO

Among different Candida species triggering vaginal candidiasis, Candida albicans is the most predominant yeast. It is commonly treated using azole drugs such as Tioconazole (TIO) and Econazole (ECO). However, their low water solubility may affect their therapeutic efficiency. Therefore, the aim of this research was to produce a novel chitosan nanocapsule based delivery system comprising of TIO or ECO and to study their suitability in vaginal application. These systems were characterized by their physicochemical properties, encapsulation efficiency, in vitro release, storage stability, cytotoxicity, and in vitro biological activity. Both nanocapsules loaded with TIO (average hydrodynamic size of 146.8 ± 0.8 nm, zeta potential of +24.7 ± 1.1 mV) or ECO (average hydrodynamic size of 127.1 ± 1.5 nm, zeta potential of +33.0 ± 1.0 mV) showed excellent association efficiency (99% for TIO and 87% for ECO). The analysis of size, polydispersity index, and zeta potential of the systems at 4, 25, and 37 °C (over a period of two months) showed the stability of the systems. Finally, the developed nanosystems presented fungicidal activity against C. albicans at non-toxic concentrations (studied on model human skin cells). The results obtained from this study are the first step in the development of a pharmaceutical dosage form suitable for the treatment of vaginal candidiasis.


Assuntos
Antifúngicos/administração & dosagem , Quitosana/química , Portadores de Fármacos/química , Nanopartículas/química , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Fenômenos Químicos , Sistemas de Liberação de Medicamentos , Liberação Controlada de Fármacos , Estabilidade de Medicamentos , Econazol/administração & dosagem , Econazol/química , Imidazóis/administração & dosagem , Imidazóis/química , Testes de Sensibilidade Microbiana , Estrutura Molecular , Nanocápsulas/química , Nanopartículas/ultraestrutura
5.
Sci Total Environ ; 670: 770-778, 2019 Jun 20.
Artigo em Inglês | MEDLINE | ID: mdl-30921710

RESUMO

Enantiomer stability was investigated in this work for the first time for duloxetine and econazole in individual solutions and their mixtures under the standardized ecotoxicity test experimental conditions for Daphnia magna and abiotic conditions. Real (and not nominal) enantiomer concentrations were employed for calculations since their determination was achieved by Capillary Electrophoresis. Relevant differences were found in stability profiles for both drugs in any case. Toxicity was evaluated for the first time in this work for mixtures of duloxetine and econazole on Daphnia magna. Dose-effect parameters were calculated at different exposure times (24, 48, and 72 h) showing a significant inhibition of daphnids mobility when increasing the incubation time. Combination index values enabled to obtain the type and level of interaction of drugs with the organism. A strong synergism was observed at 48 h exposure time and any effect level, which demonstrated the high toxicity of the drug mixture compared with the individual drug solutions. These results were corroborated when evaluating the oxidative stress using fluorescence images.


Assuntos
Cloridrato de Duloxetina/toxicidade , Econazol/toxicidade , Poluentes Químicos da Água/toxicidade , Animais , Daphnia , Eletroforese Capilar , Estresse Oxidativo , Estereoisomerismo , Testes de Toxicidade Aguda
6.
Pharm Dev Technol ; 24(6): 689-699, 2019 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-30712434

RESUMO

The purpose of this work was to design and characterize a topical formulation of econazole nitrate (EN) with potential for treating Raynaud's phenomenon (RP). Four topical dosage forms (F1_topical solution, F2_HPMC or hydroxypropyl methylcellulose dispersion, F3_VersaBase® cream, and F4_Lipoderm® Activemax™ Cream) containing 3% w/w EN were prepared and characterized for drug content, pH, viscosity, spreadability, drug crystallinity, stability, and in vitro permeation using Franz cells across pig ear skin, and results were compared to the 1% marketed EN cream. All four formulations had acceptable physical and visual characteristics required for topical application, with 3% w/w EN. The order of amount of drug permeated from highest to lowest was F2 (10.27%) > F4 (2.47%) > F1 (2.28%) > F3 (1.47%) > marketed formulation (0.22%). Formulation F2 showed better penetration of the drug into the stratum corneum, epidermis, and dermis layers. The drug concentration in the stratum corneum and epidermis was approximately 10-20 times higher with F2 compared to the marketed formulation. All formulations were found to be stable for up to 6 months. All four EN formulations were found to be better than the 1% marketed cream. Formulation F2_HPMC dispersion could be further explored as a treatment option for RP.


Assuntos
Inibidores de 14-alfa Desmetilase/administração & dosagem , Antifúngicos/administração & dosagem , Econazol/administração & dosagem , Veículos Farmacêuticos/química , Doença de Raynaud/tratamento farmacológico , Inibidores de 14-alfa Desmetilase/farmacocinética , Administração Tópica , Animais , Antifúngicos/farmacocinética , Cristalização , Composição de Medicamentos/métodos , Econazol/farmacocinética , Humanos , Derivados da Hipromelose/química , Doença de Raynaud/metabolismo , Absorção Cutânea , Suínos
7.
Toxicol Sci ; 169(1): 209-223, 2019 05 01.
Artigo em Inglês | MEDLINE | ID: mdl-30698772

RESUMO

Tebuconazole and Econazole are triazole and imidazole fungicides currently used worldwide. Although their reproductive toxicity in mammals has been described, their effect on male reproductive systems has been poorly investigated. As humans may be exposed to different azole compounds simultaneously, the combinational in vitro toxicity of Tebuconazole and Econazole (MIX) in mouse Sertoli TM4 cells was investigated. This study demonstrates that Tebuconazole (40 µM) and Econazole (20 µM) act synergistically in mediating decrease of mitochondrial membrane potential (ΔΨm) and changes in mitochondrial morphology. These events were associated with ATP depletion, cell cycle arrest, and sequential activation of autophagy and apoptosis. Remarkable differences on other parameters such as AMP/ATP ratio and adenylate energy charge were observed. Pharmacological inhibition of autophagy by bafilomycin A1 leads to enhanced MIX-induced apoptosis suggesting an adaptive cytoprotective function for MIX-modulated autophagy. Finally, a possible role of AMPK/ULK1 axis in mediating adaptive signalling cascades in response to energy stress was hypothesized. Consistently, ULK1 Ser 555 phosphorylation occurred in response to AMPK (Thr 172) activation. In conclusion, Tebuconazole and Econazole combination, at concentrations relevant for dermal and clinical exposure, induces a severe mitochondrial stress in SCs. Consequently, a prolonged exposure may affect the ability of the cells to re-establish homeostasis and trigger apoptosis.


Assuntos
Antifúngicos/toxicidade , Apoptose/efeitos dos fármacos , Autofagia/efeitos dos fármacos , Econazol/toxicidade , Metabolismo Energético/efeitos dos fármacos , Fungicidas Industriais/toxicidade , Mitocôndrias/efeitos dos fármacos , Células de Sertoli/efeitos dos fármacos , Estresse Fisiológico/efeitos dos fármacos , Triazóis/toxicidade , Proteínas Quinases Ativadas por AMP/metabolismo , Animais , Proteína Homóloga à Proteína-1 Relacionada à Autofagia/metabolismo , Pontos de Checagem do Ciclo Celular/efeitos dos fármacos , Linhagem Celular , Proliferação de Células/efeitos dos fármacos , Relação Dose-Resposta a Droga , Sinergismo Farmacológico , Masculino , Potencial da Membrana Mitocondrial/efeitos dos fármacos , Camundongos , Mitocôndrias/metabolismo , Mitocôndrias/patologia , Células de Sertoli/metabolismo , Células de Sertoli/patologia , Transdução de Sinais
9.
Pharm Nanotechnol ; 6(3): 171-179, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-30101725

RESUMO

BACKGROUND: Transdermal drug delivery is an attractive approach for both local and systemic therapeutics of various diseases. Transdermal drug delivery systems show various advantages like reduction of local irritation, prevention of first-pass hepatic metabolism, and bioavailability enhancement of bioactive molecules over conventional drug delivery systems. OBJECTIVE: The main objective of the present research work was to develop and characterize (in-vitro and ex-vivo) econazole nitrate loaded transethosomes and their comparison with marketed cream of econazole nitrate [Ecoderm, Brown and Burk Pharmaceutical (Pvt.) Ltd., Bengaluru, India] for effective transdermal delivery. METHOD: Transethosomes loaded with econazole nitrate were developed by homogenization method and evaluated for entrapment (%), vesicular size, zeta potential, polydispersity index (PDI), and invitro drug release. Furthermore, optimized econazole nitrate loaded transethosomes were added to Carbopol 934 gel and this gel was evaluated for viscosity, pH, drug content, ex-vivo skin permeation and retention studies followed by in-vitro antifungal activity against C. albicans fungus. RESULTS: The optimized transethosomes loaded with econazole nitrate showed vesicle size of 159.3 ± 4.3 nm, entrapment efficiency about 78.3 ± 2.8%, acceptable colloidal properties like (zeta potential = -27.13 ± 0.33 mV, PDI = 0.244 ± 0.045), approximately 57.56 ± 2.33% drug release up to 24 h. Results of DSC analysis confirmed the encapsulation of econazole nitrate inside transethosomes. Optimized transethosomes showed drug release following zero order through diffusion mechanism. Transethosomal gel showed high drug content (92.35 ± 0.63%) and acceptable values of pH (5.68 ± 0.86) or viscosity (10390 ± 111 cPs). Transethosomal gel showed less ex-vivo skin penetration (17.53 ± 1.20%), high ex-vivo skin retention (38.75 ± 2.88%), and high in-vitro antifungal activity compared to the marketed cream of econazole nitrate. CONCLUSION: Therefore, it can be concluded that econazole nitrate loaded transethosomes are effective to deliver econazole nitrate transdermally in a controlled fashion for effective elimination of cutaneous candidiasis.


Assuntos
Antifúngicos/administração & dosagem , Portadores de Fármacos/administração & dosagem , Econazol/administração & dosagem , Acrilatos/administração & dosagem , Acrilatos/química , Administração Cutânea , Animais , Antifúngicos/química , Candida albicans/efeitos dos fármacos , Portadores de Fármacos/química , Liberação Controlada de Fármacos , Econazol/química , Pele/metabolismo , Absorção Cutânea , Suínos
10.
Dokl Biochem Biophys ; 480(1): 152-154, 2018 May.
Artigo em Inglês | MEDLINE | ID: mdl-30008098

RESUMO

Using voltage-clamp technique, the involvement of epoxygenases in immunomodulatory drug glutoxim regulation of Na+ transport in frog skin was investigated. We have shown for the first time that preincubation of the frog skin with epoxygenase inhibitors econazole or proadifen almost completely inhibits the stimulatory effect of glutoxim on Na+ transport. The data suggest the involvement of the enzymes and/or products of epoxygenase oxidation pathway of arachidonic acid metabolism in glutoxim effect on Na+ transport in frog skin epithelium.


Assuntos
Econazol/farmacologia , Inibidores Enzimáticos/farmacologia , Oligopeptídeos , Oxirredutases/antagonistas & inibidores , Pele/metabolismo , Sódio/metabolismo , Animais , Transporte de Íons/efeitos dos fármacos , Oligopeptídeos/farmacocinética , Oligopeptídeos/farmacologia , Rana temporaria
12.
J Mater Sci Mater Med ; 29(5): 70, 2018 May 11.
Artigo em Inglês | MEDLINE | ID: mdl-29752591

RESUMO

While antibiotic-eluting polymethylmethacrylate space maintainers have shown efficacy in the treatment of bacterial periprosthetic joint infection and osteomyelitis, antifungal-eluting space maintainers are associated with greater limitations for treatment of fungal musculoskeletal infections including limited elution concentration and duration. In this study, we have designed a porous econazole-eluting space maintainer capable of greater inhibition of fungal growth than traditional solid space maintainers. The eluted econazole demonstrated bioactivity in a concentration-dependent manner against the most common species responsible for fungal periprosthetic joint infection as well as staphylococci. Lastly, these porous space maintainers retain compressive mechanical properties appropriate to maintain space before definitive repair of the joint or bony defect.


Assuntos
Antifúngicos/química , Materiais Biocompatíveis , Econazol/química , Micoses/tratamento farmacológico , Infecções Relacionadas à Prótese/tratamento farmacológico , Antifúngicos/farmacologia , Aspergillus fumigatus/efeitos dos fármacos , Candida albicans/efeitos dos fármacos , Econazol/farmacologia , Teste de Materiais , Polimetil Metacrilato , Porosidade , Staphylococcus aureus/efeitos dos fármacos
13.
Drug Deliv ; 25(1): 938-949, 2018 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-29658325

RESUMO

Fungal keratitis (FK) remains a severe eye disease, and effective therapies are limited by drug shortages and critical ocular barriers. Despite the high antifungal potency and broad spectrum of econazole, its strong irritant and insolubility in water hinder its ocular application. We designed and fabricated a new drug delivery system based on a polymeric vector for the ocular antifungal application of econazole. This novel system integrates the advantages of its constituent units and exhibits superior comprehensive performance. Using the new system, drug content was significantly increased more than 600 folds. The results of in vivo and in vitro experiments demonstrated that the econazole-loaded formulation exhibited significantly enhanced corneal penetration after a single topical ocular administration, excellent antifungal activity, and good tolerance in rabbits. Drug concentrations and ocular relative bioavailability in the cornea were 59- and 29-time greater than those in the control group, respectively. Following the topical administration of one eye drop (50 µL of 0.3% w/v econazole) in fungus-infected rabbits, a high concentration of antimycotic drugs in the cornea and aqueous humor was sustained and effective for 4 h. The mechanism of corneal penetration was also explored using dual fluorescent labeling. This novel drug delivery system is a promising therapeutic approach for oculomycosis and could serve as a candidate strategy for use with various hydrophobic drugs to overcome barriers in the treatment of many other ocular diseases.


Assuntos
Antifúngicos/administração & dosagem , Córnea/metabolismo , Portadores de Fármacos , Econazol/administração & dosagem , Infecções Oculares Fúngicas/tratamento farmacológico , Ceratite/tratamento farmacológico , Polímeros/química , Administração Oftálmica , Animais , Antifúngicos/química , Antifúngicos/farmacocinética , Disponibilidade Biológica , Candida/efeitos dos fármacos , Candida/crescimento & desenvolvimento , Preparações de Ação Retardada , Composição de Medicamentos , Econazol/química , Econazol/metabolismo , Infecções Oculares Fúngicas/microbiologia , Fusarium/efeitos dos fármacos , Fusarium/crescimento & desenvolvimento , Ceratite/microbiologia , Masculino , Camundongos Endogâmicos C57BL , Soluções Oftálmicas , Permeabilidade , Coelhos , Solubilidade , Tecnologia Farmacêutica/métodos , Distribuição Tecidual , Viscosidade
14.
Int J Pharm ; 541(1-2): 72-80, 2018 Apr 25.
Artigo em Inglês | MEDLINE | ID: mdl-29458206

RESUMO

AIM: Development of mucoadhesive self-emulsifying drug delivery systems (SEDDS) providing a prolonged ocular residence time for poorly soluble active pharmaceutical ingredient. METHODS: l-Cysteine was covalently linked to 6-mercaptonicotinamide. The obtained ligand, Cysteine-6-mercaptonicotinamide (Cys-6-MNA) was attached to Eudragit® L100-55 via a carbodiimide mediated amide bond formation. The resulting entirely S-protected thiolated Eudragit® L100-55 was characterized regarding the degree of modification as well as stability toward oxidation in the presence of strong oxidizing agent (H2O2). The S-protected thiolated Eudragit® L100-55 was incorporated into SEDDS via hydrophobic ion pairing with benzalkonium chloride (BAK) in a concentration of 2% (m/m). S-protected thiolated Eudragit® L100-55-BAK ion pair SEDDS (S-protected thiolated EU-BAK SEDDS) were characterized regarding their physicochemical and mucoadhesive properties. Econazole nitrate (EN) was incorporated into SEDDS in concentration of 1% (m/m) and in vitro drug release was assessed. Furthermore, toxicity study was performed on procine corneas via resazurin assay. RESULTS: The entirely S-protected thiolated Eudragit® L100-55 exhibited 282 ±â€¯78.25 µmol of MNA per gram of polymer. Ellman's test confirmed no free thiol groups and stability study showed no significant increase in dynamic viscosity overtime. The droplet size of developed SEDDS in simulated lacrimal fluid was below 100 nm with polydispersity index below 0.3. S-protected thiolated EU-BAK SEDDS exhibited 2.5-fold higher mucoadhesive properties than blank SEDDS on ocular mucosa. S-protected thiolated EU-BAK SEDDS showed sustained EN release over period of 8 h and no pronounced corneal toxicity in 0.5% (m/v) concentration. CONCLUSION: Accordingly, these mucoadhesive SEDDS can be considered as promising ocular delivery system for EN.


Assuntos
Antifúngicos/administração & dosagem , Córnea/metabolismo , Sistemas de Liberação de Medicamentos/métodos , Econazol/administração & dosagem , Membrana Mucosa/metabolismo , Resinas Acrílicas/química , Administração Oftálmica , Animais , Antifúngicos/química , Compostos de Benzalcônio/química , Cisteína/química , Preparações de Ação Retardada/administração & dosagem , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos , Econazol/química , Emulsões , Interações Hidrofóbicas e Hidrofílicas , Modelos Animais , Solubilidade , Compostos de Sulfidrila/química , Suínos , Fatores de Tempo
15.
J Drugs Dermatol ; 17(2): 229-232, 2018 Feb 01.
Artigo em Inglês | MEDLINE | ID: mdl-29462232

RESUMO

BACKGROUND: Tinea pedis is the most common dermatophyte infection. Treatment is critical to alleviate pruritic symptoms, to reduce the risk for secondary bacterial infection, and to limit the spread of infection to other body sites or other individuals. The objective of this study was to compare the abilities of econazole nitrate topical foam, 1% and ketoconazole cream (2%) to reduce pruritus, thus improving quality of life, and to determine patient preference for the foam product versus the cream product in patients with interdigital tinea pedis. STUDY DESIGN: A single-center, investigator-blinded, observational pilot study was conducted to compare econazole nitrate topical foam (1%) to ketoconazole cream (2%). In this split-body study, 20 subjects received both econazole nitrate topical foam and ketoconazole cream and applied the medications daily to either the right or left foot for 14 days. Improvements in patient quality of life (pruritus) and patient preference were measured using the pruritus visual analog scale (VAS), Skindex-16, and patient preference questionnaires. RESULTS: Nineteen subjects completed the study and one subject was lost to follow-up. Reductions in VAS scores of econazole nitrate topical foam were significantly greater than those of ketoconazole cream, indicating the superiority of the econazole nitrate foam in reducing pruritus. Skindex-16 data showed significant reductions in total scores and individual domains, including patient symptom, emotional, and functional domains, by the final visit. Since each subject received both medications the questionnaire was not medication-specific. Responses to patient preference questionnaires showed that econazole nitrate topical foam,1% was rated as "good" or "excellent" in all measures assessed. One adverse event was noted. CONCLUSION: In patients with interdigital tinea pedis, application of econazole nitrate topical foam 1% twice daily for two weeks was clinically effective and significantly superior to ketoconazole cream 2% in reducing pruritus. J Drugs Dermatol. 2018;17(2):229-232.


Assuntos
Antifúngicos/administração & dosagem , Econazol/administração & dosagem , Tinha dos Pés/diagnóstico , Tinha dos Pés/tratamento farmacológico , Administração Tópica , Adolescente , Adulto , Idoso , Composição de Medicamentos , Feminino , Seguimentos , Humanos , Masculino , Pessoa de Meia-Idade , Projetos Piloto , Método Simples-Cego , Resultado do Tratamento , Adulto Jovem
16.
J Pharm Sci ; 107(5): 1342-1351, 2018 05.
Artigo em Inglês | MEDLINE | ID: mdl-29305870

RESUMO

Econazole is a feasible alternative treatment in the management of fungal keratitis. Nevertheless, its low water solubility is considered the main limitation to the incorporation into ophthalmic formulations. In this work, econazole nitrate is solubilized by using cyclodextrins to achieve an optimum therapeutic concentration. Phase solubility diagrams suggest α-cyclodextrin as the most effective cyclodextrin and later the inclusion complex formed with this one was characterized in solution by 1D, 2D-NMR, and molecular modeling. Econazole-α-cyclodextrin inclusion complex was included in 2 types of ocular hydrogels: a natural polysaccharides ion-sensitive hydrogel and a hyaluronic acid hydrogel. Both of them show no ocular irritation in the hen's egg test on chorioallantoic membrane assay and a controlled econazole release over time. Permeability studies suggest that hydrogels do not modify the econazole nitrate permeability through bovine cornea in comparison with an econazole-α-cyclodextrin inclusion complex solution. Finally, ocular biopermanence studies performed using positron emission tomography show these hydrogels present a high retention time on the eye. Results suggest the developed formulations have a high potential as vehicles for the econazole topical ocular administration as fungal keratitis treatment.


Assuntos
Antifúngicos/administração & dosagem , Preparações de Ação Retardada/química , Econazol/administração & dosagem , Hidrogéis/química , Ceratite/tratamento farmacológico , alfa-Ciclodextrinas/química , Administração Oftálmica , Animais , Antifúngicos/farmacocinética , Antifúngicos/farmacologia , Bovinos , Galinhas , Córnea/metabolismo , Córnea/microbiologia , Composição de Medicamentos , Econazol/farmacocinética , Econazol/farmacologia , Fungos/efeitos dos fármacos , Ceratite/metabolismo , Ceratite/microbiologia , Solubilidade
17.
Nat Struct Mol Biol ; 25(1): 53-60, 2018 01.
Artigo em Inglês | MEDLINE | ID: mdl-29323279

RESUMO

The transient receptor potential vanilloid 5 (TRPV5) channel is a member of the transient receptor potential (TRP) channel family, which is highly selective for Ca2+, that is present primarily at the apical membrane of distal tubule epithelial cells in the kidney and plays a key role in Ca2+ reabsorption. Here we present the structure of the full-length rabbit TRPV5 channel as determined using cryo-EM in complex with its inhibitor econazole. This structure reveals that econazole resides in a hydrophobic pocket analogous to that occupied by phosphatidylinositides and vanilloids in TRPV1, thus suggesting conserved mechanisms for ligand recognition and lipid binding among TRPV channels. The econazole-bound TRPV5 structure adopts a closed conformation with a distinct lower gate that occludes Ca2+ permeation through the channel. Structural comparisons between TRPV5 and other TRPV channels, complemented with molecular dynamics (MD) simulations of the econazole-bound TRPV5 structure, allowed us to gain mechanistic insight into TRPV5 channel inhibition by small molecules.


Assuntos
Microscopia Crioeletrônica , Econazol/farmacologia , Canais de Cátion TRPV/antagonistas & inibidores , Canais de Cátion TRPV/química , Animais , Cálcio/química , Membrana Celular/química , Epitopos/química , Humanos , Interações Hidrofóbicas e Hidrofílicas , Íons , Simulação de Dinâmica Molecular , Mutação , Fosfatidilinositóis/química , Conformação Proteica , Coelhos , Ratos , Xenopus laevis
18.
Med Chem ; 14(3): 311-319, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29032761

RESUMO

BACKGROUND: Fused five-membered heterocyclic rings containing bridgehead nitrogen atom are particularly versatile in the field of medicinal chemistry because of their different biological activities. Among them, the imidazo[2,1-b]thiazole is an attractive fused heterocyclic core that has been extensively studied. OBJECTIVE: The aim of the current study was to study the therapeutic applications of imidazo[2,1- b]thiazole derivatives as antimicrobial agents for the treatment of genitourinary infections. METHOD: A traditional synthetic methodology was involved to obtain a small series of imidazothiazole derivatives. RESULTS: Herein, we report the antimicrobial activity of the imidazo[2,1-b]thiazole or imidazo[2,1- b]thiazolidine derivatives against selected fungi, Gram-positive and Gram-negative bacteria. Moreover, experiments were carried out to investigate the interference towards the endogenous microbiota. CONCLUSION: The most interesting of the series are the thiocyano derivatives (19, 23) showing a good profile for the treatment of genitourinary infections: a spectrum of activity covering both bacteria and fungi together with a reduced impact versus critical lines of Lactobacillus exerting defense against pathogens.


Assuntos
Antibacterianos/farmacologia , Imidazóis/farmacologia , Tiazóis/farmacologia , Antibacterianos/síntese química , Antifúngicos/síntese química , Antifúngicos/farmacologia , Antineoplásicos/síntese química , Antineoplásicos/farmacologia , Bifidobacterium/efeitos dos fármacos , Econazol/farmacologia , Células HeLa , Humanos , Imidazóis/síntese química , Lactobacillus/efeitos dos fármacos , Testes de Sensibilidade Microbiana , Tiazóis/síntese química , Sistema Urogenital/microbiologia
19.
J AOAC Int ; 101(4): 981-991, 2018 Jul 01.
Artigo em Inglês | MEDLINE | ID: mdl-28903833

RESUMO

Two specific, sensitive, and precise stability-indicating chromatographic methods have been developed for the determination of triamcinolone acetonide (TMC) and its coformulated drug, econazole nitrate (ECZ), in the presence of TMC impurities and degradation products. The first method was based on HPTLC-spectrodensitometry in which resolution and quantitation was achieved by using silica gel 60 F254 HPTLC plates and an ethyl acetate-tetrahydrofuran-ammonia mobile phase (10.0 + 7.0 + 0.1, v/v/v). The second method was a reversed-phase HPLC method in which separation was achieved using an acetonitrile-methanol-0.05 M potassium dihydrogen phosphate mobile phase, pH 3.0 (25.0 + 15.0 + 60.0, v/v/v). In both methods, the separated components were detected at 225 nm. Validation of both methods was conducted in compliance with International Conference on Harmonization (ICH) guidelines, and system suitability was confirmed. The linearity ranges were 0.20-28.00 and 0.50-55.00 µg/band for TMC and ECZ by HPTLC, whereas for HPLC, the range was 0.05-30.00 and 1.00-40.00 µg/mL for both drugs, respectively. The methods were successfully applied for the analysis of a pharmaceutical formulation and were compared with the reported method with no significant difference.


Assuntos
Cromatografia Líquida de Alta Pressão/métodos , Cromatografia em Camada Delgada/métodos , Triancinolona Acetonida/análise , Cromatografia de Fase Reversa/métodos , Combinação de Medicamentos , Contaminação de Medicamentos , Estabilidade de Medicamentos , Econazol/análise , Reprodutibilidade dos Testes , Sensibilidade e Especificidade , Triancinolona Acetonida/química
20.
Colloids Surf B Biointerfaces ; 163: 73-82, 2018 Mar 01.
Artigo em Inglês | MEDLINE | ID: mdl-29278802

RESUMO

In this paper we developed an innovative, effective and rapid one-step approach to crosslink mucoadhesive gelatin films for buccal drug delivery. The method, which involves the application of non-equilibrium pressure plasma for 3 or 5 minutes/side, was compared with a classical approach based on the use of a chemical crosslinking agent, namely genipin. Econazole nitrate (ECN), an imidazole antifungal agent used for the treatment of skin infections and mucosal candidiasis, was selected as model drug. X-Ray Diffraction characterization performed on the drug-containing gelatin films revealed that ECN undergoes to a topotactic transformation into Econazole (EC) immediately after mixing with gelatin suggesting the occurrence of an acid-base reaction between drug and gelatin during film processing. Plasma treatment, as well as genipin crosslinking, did not provoke any further variation of EC structure. However, plasma exposure significantly improved films adhesiveness and allowed to reach mucoadhesive strength values more than double with respect to those obtained with genipin, ascribable to the presence of polar and hydrophilic groups on the plasma treated film's surface. A residence time of at least 48 h was obtained by properly selecting the plasma exposure times. These results, together with the in-vitro data showing retention of antifungal efficacy against a strain of Candida albicans, demonstrated that plasma treatment was a valid and rapid alternative, easy to scale-up, to chemical crosslinking methods for the production of highly mucoadhesive gelatin-based films.


Assuntos
Reagentes para Ligações Cruzadas/química , Portadores de Fármacos , Gelatina/química , Iridoides/química , Gases em Plasma/química , Adesividade , Administração Bucal , Animais , Antifúngicos/química , Antifúngicos/farmacologia , Pressão Atmosférica , Candida albicans/efeitos dos fármacos , Candida albicans/crescimento & desenvolvimento , Composição de Medicamentos/métodos , Liberação Controlada de Fármacos , Econazol/química , Econazol/farmacologia , Cinética , Mucosa Bucal/efeitos dos fármacos , Mucosa Bucal/metabolismo , Suínos , Resistência à Tração
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