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1.
Int J Mol Sci ; 25(10)2024 May 09.
Artigo em Inglês | MEDLINE | ID: mdl-38791175

RESUMO

The modified release of active substances such as chlorzoxazone from matrix tablets, based on Kollidon®SR and chitosan, depends both on the drug solubility in the dissolution medium and on the matrix composition. The aim of this study is to obtain some new oral matrix tablet formulations, based on Kollidon®SR and chitosan, in order to optimize the low-dose oral bioavailability of chlorzoxazone, a non-steroidal anti-inflammatory drug of class II Biopharmaceutical Classification System. Nine types of chlorzoxazone matrix tablets were obtained using the direct compression method by varying the components ratio as 1:1, 1:2, and 1:3 chlorzoxazone/excipients, 20-40 w/w % Kollidon®SR, 3-7 w/w % chitosan while the auxiliary substances: Aerosil® 1 w/w %, magnesium stearate 0.5 w/w % and Avicel® up to 100 w/w % were kept in constant concentrations. Pharmaco-technical characterization of the tablets included the analysis of flowability and compressibility properties (flow time, friction coefficient, angle of repose, Hausner ratio, and Carr index), and pharmaco-chemical characteristics (such as mass and dose uniformity, thickness, diameter, mechanical strength, friability, softening degree, and in vitro release profiles). Based on the obtained results, only three matrix tablet formulations (F1b, F2b, and F3b, containing 30 w/w % KOL and 5 w/w % CHT, were selected and further tested. These formulations were studied in detail by Fourier-transform infrared spectrometry, X-ray diffraction, thermogravimetry, and differential scanning calorimetry. The three formulations were comparatively studied regarding the release kinetics of active substances using in vitro release testing. The results were analyzed by fitting into four representative mathematical models for the modified-release oral formulations. In vitro kinetic study revealed a complex mechanism of release occurring in two steps of drug release, the first step (0-2 h) and the second (2-36 h). Two factors were calculated to assess the release profile of chlorzoxazone: f1-the similarity factor, and f2-the factor difference. The results have shown that both Kollidon®SR and chitosan may be used as matrix-forming agents when combined with chlorzoxazone. The three formulations showed optima pharmaco-technical properties and in vitro kinetic behavior; therefore, they have tremendous potential to be used in oral pharmaceutical products for the controlled delivery of chlorzoxazone. In vitro dissolution tests revealed a faster drug release for the F2b sample.


Assuntos
Quitosana , Clorzoxazona , Preparações de Ação Retardada , Liberação Controlada de Fármacos , Interações Hidrofóbicas e Hidrofílicas , Comprimidos , Comprimidos/química , Clorzoxazona/química , Clorzoxazona/farmacocinética , Preparações de Ação Retardada/química , Preparações de Ação Retardada/farmacocinética , Quitosana/química , Solubilidade , Excipientes/química , Química Farmacêutica/métodos
2.
Int J Mol Sci ; 22(13)2021 Jun 30.
Artigo em Inglês | MEDLINE | ID: mdl-34209248

RESUMO

Starting from indomethacin (IND), one of the most prescribed non-steroidal anti-inflammatory drugs (NSAIDs), new nitric oxide-releasing indomethacin derivatives with 1,3,4-oxadiazole-2-thiol scaffold (NO-IND-OXDs, 8a-p) have been developed as a safer and more efficient multitarget therapeutic strategy. The successful synthesis of designed compounds (intermediaries and finals) was proved by complete spectroscopic analyses. In order to study the in silico interaction of NO-IND-OXDs with cyclooxygenase isoenzymes, a molecular docking study, using AutoDock 4.2.6 software, was performed. Moreover, their biological characterization, based on in vitro assays, in terms of thermal denaturation of serum proteins, antioxidant effects and the NO releasing capacity, was also performed. Based on docking results, 8k, 8l and 8m proved to be the best interaction for the COX-2 (cyclooxygense-2) target site, with an improved docking score compared with celecoxib. Referring to the thermal denaturation of serum proteins and antioxidant effects, all the tested compounds were more active than IND and aspirin, used as references. In addition, the compounds 8c, 8h, 8i, 8m, 8n and 8o showed increased capacity to release NO, which means they are safer in terms of gastrointestinal side effects.


Assuntos
Ciclo-Oxigenase 2/química , Indometacina , Simulação de Acoplamento Molecular , Óxido Nítrico/química , Oxidiazóis , Humanos , Indometacina/síntese química , Indometacina/química , Oxidiazóis/síntese química , Oxidiazóis/química
3.
Molecules ; 27(1)2021 Dec 30.
Artigo em Inglês | MEDLINE | ID: mdl-35011449

RESUMO

Silver nanoparticles synthesized using plant extracts as reducing and capping agents showed various biological activities. In the present study, colloidal silver nanoparticle solutions were produced from the aqueous extracts of Picea abies and Pinus nigra bark. The phenolic profile of bark extracts was analyzed by liquid chromatography coupled to mass spectrometry. The synthesis of silver nanoparticles was monitored using UV-Vis spectroscopy by measuring the Surface Plasmon Resonance band. Silver nanoparticles were characterized by attenuated total reflection Fourier transform infrared spectroscopy, Raman spectroscopy, dynamic light scattering, scanning electron microscopy, energy dispersive X-ray and transmission electron microscopy analyses. The antimicrobial and cytogenotoxic effects of silver nanoparticles were evaluated by disk diffusion and Allium cepa assays, respectively. Picea abies and Pinus nigra bark extract derived silver nanoparticles were spherical (mean hydrodynamic diameters of 78.48 and 77.66 nm, respectively) and well dispersed, having a narrow particle size distribution (polydispersity index values of 0.334 and 0.224, respectively) and good stability (zeta potential values of -10.8 and -14.6 mV, respectively). Silver nanoparticles showed stronger antibacterial, antifungal, and antimitotic effects than the bark extracts used for their synthesis. Silver nanoparticles obtained in the present study are promising candidates for the development of novel formulations with various therapeutic applications.


Assuntos
Anti-Infecciosos/farmacologia , Antineoplásicos/farmacologia , Nanopartículas Metálicas/química , Casca de Planta/química , Extratos Vegetais/química , Prata/química , Anti-Infecciosos/síntese química , Anti-Infecciosos/química , Antineoplásicos/síntese química , Antineoplásicos/química , Fenômenos Químicos , Técnicas de Química Sintética , Química Verde , Nanopartículas Metálicas/ultraestrutura , Fenóis/química , Análise Espectral
4.
Polymers (Basel) ; 16(15)2024 Jul 30.
Artigo em Inglês | MEDLINE | ID: mdl-39125186

RESUMO

Miscarriage is defined as the loss of a pregnancy before 24 weeks and administration of progesterone in pregnancy has considerably decreased the risk of premature birth. Progesterone (PGT) starting from the luteal phase stabilizes pregnancy, promotes differentiation of the endometrium, and facilitates the implantation of the embryo. Within the present study, novel hybrid hydrogels based on chitosan methacrylate (CHT), hyaluronic acid (HA), and poly(N-isopropylacrylamide) (PNIPAAm) for vaginal delivery of progesterone were evaluated. The hydrogels were characterized by Fourier transform infrared spectroscopy (FTIR) and scanning electron microscopy (SEM) for structural identity assessment and evaluation of their morphological aspects. The ability to swell, the release capacity, enzymatic degradation, cytotoxicity, and mucoadhesion were also reported. The characterized hydrogels demonstrated mucoadhesive properties in contact with the vaginal tissue of swine and bovine origin as substrates, and biodegradability and controlled release in a simulated vaginal environment. Cytocompatibility tests confirmed the ability of the hydrogels and progesterone to support cell viability and growth. The results showed pH-dependent behavior, controlled drug release, good cytocompatibility, and mucoadhesive properties. The hydrogels with higher chitosan amounts demonstrated better bioadhesive properties. This study provides insights into the potential of these hydrogels for the controlled vaginal delivery of progesterone, with promising therapeutic effects and no cytotoxicity observed. The experimental results indicated that a composition with a moderate content of PNIPAAm was suitable for the controlled delivery of progesterone.

5.
Antioxidants (Basel) ; 12(4)2023 Mar 24.
Artigo em Inglês | MEDLINE | ID: mdl-37107172

RESUMO

In recent years, phytofunctionalized AgNPs have attracted great interest due to their remarkable biological activities. In the present study, AgNPs were synthesized using Abies alba and Pinus sylvestris bark extracts. The chemical profile of these bark extracts was analyzed by LC-HRMS/MS. As a first step, the synthesis parameters (pH, AgNO3 concentration, ratio of bark extract and AgNO3, temperature, and reaction time) were optimized. The synthesized AgNPs were characterized by ATR-FTIR spectroscopy, DLS, SEM, EDX, and TEM. Their antioxidant, cytotoxic, and antibacterial properties were evaluated by the DPPH, ABTS, MTT, and broth microdilution assays, respectively. Abies alba and Pinus sylvestris bark extract-derived AgNPs were well-dispersed, spherical, small (average particle size of 9.92 and 24.49 nm, respectively), stable (zeta potential values of -10.9 and -10.8 mV, respectively), and cytotoxic to A-375 human malignant melanoma cells (IC50 = 2.40 ± 0.21 and 6.02 ± 0.61 µg/mL, respectively). The phytosynthesized AgNPs also showed antioxidant and antibacterial effects.

6.
Biomed Pharmacother ; 139: 111678, 2021 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-33964802

RESUMO

In this study we present design and synthesis of nineteen new nitric oxide-releasing indomethacin derivatives with 1,3-thiazolidine-4-one scaffold (NO-IND-TZDs) (6a-s), as a new safer and efficient multi-targets strategy for inflammatory diseases. The chemical structure of all synthesized derivatives (intermediaries and finals) was proved by NMR and mass spectroscopic analysis. In order to study the selectivity of NO-IND-TZDs for COX isoenzymes (COX-1 and COX-2) a molecular docking study was performed using AutoDock 4.2.6 software. Based on docking results, COX-2 inhibitors were designed and 6o appears as the most selective derivative which showed an improved selective index compared with indomethacin (IND) and diclofenac (DCF), used as reference drugs. The biological evaluation of 6a-s, using in vitro assays has included the anti-inflammatory and antioxidant effects as well as the nitric oxide (NO) release. Referring to the anti-inflammatory effects, the most active compound was 6i, which was more active than IND and aspirin (ASP) in term of denaturation effect, on bovine serum albumin (BSA), as indirect assay to predict the anti-inflammatory effect. An appreciable anti-inflammatory effect, in reference with IND and ASP, was also showed by 6k, 6c, 6q, 6o, 6j, 6d. The antioxidant assay revealed the compound 6n as the most active, being 100 times more active than IND. The compound 6n showed also the most increase capacity to release NO, which means is safer in terms of gastro-intestinal side effects. The ADME-Tox study revealed also that the NO-IND-TZDs are generally proper for oral administration, having optimal physico-chemical and ADME properties. We can conclude that the compounds 6i and 6n are promising agents and could be included in further investigations to study in more detail their pharmaco-toxicological profile.


Assuntos
Indometacina/análogos & derivados , Indometacina/farmacologia , Doadores de Óxido Nítrico/farmacologia , Tiazolidinas/farmacologia , Anti-Inflamatórios não Esteroides/farmacologia , Antioxidantes/síntese química , Antioxidantes/farmacologia , Aspirina/farmacologia , Simulação por Computador , Ciclo-Oxigenase 1/metabolismo , Ciclo-Oxigenase 2/metabolismo , Diclofenaco/farmacologia , Desenho de Fármacos , Sequestradores de Radicais Livres/química , Sequestradores de Radicais Livres/farmacologia , Humanos , Indometacina/química , Espectroscopia de Ressonância Magnética , Simulação de Acoplamento Molecular , Doadores de Óxido Nítrico/química , Doadores de Óxido Nítrico/toxicidade , Soroalbumina Bovina/química , Relação Estrutura-Atividade
7.
Rev Med Chir Soc Med Nat Iasi ; 120(3): 715-9, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-30152660

RESUMO

Aim: Drug release from modified-release matrix tablets made of Kollidon® SR and Chitosan is dependent on its degree of solubility in the dissolution medium as well as on the matrix forming polymer. By complexing hydrochloride amiodarone with hydroxypropyl-ß-cyclodextrin, an inclusion complex was obtained, which showed an increase in solubility by more than 200%. The complex was used to obtain modified-release matrix tablets based on Kollidon® SR and Chitosan. Materials and Methods: Matrix tablets were obtained through direct compression method of non-complexed amiodarone and inclusion complex, and they were marked F1 and F10, respectively. The two formulations were studied comparatively in terms of release kinetics of the active substance through in vitro drug release tests. Those tests were conducted using a paddle apparatus II for 12 hours and two gastrointestinal simulation liquids with different pH values relevant for oral administration - 2 hours at pH 1.2 and 10 hours at pH 6.8. The release of hydrochloride amiodarone was quantified using a validated HPLC method. Two factors were calculated to assess the release profile of amiodarone: the similarity factor f1 and difference factor f2. Results: The increase in Kollidon® SR concentration resulted in a slower release of amiodarone at both pH values. The use of Chitosan resulted in a decrease of AMD release only at pH 6.8. Conclusions: The similarities between the two release profiles of AMD were confirmed by the values of the similarity factor (f1 = 43.697) and difference factor f2 (f2 = 68.263).


Assuntos
Amiodarona/química , beta-Ciclodextrinas/química , Química Farmacêutica , Quitosana/química , Preparações de Ação Retardada , Concentração de Íons de Hidrogênio , Técnicas In Vitro , Povidona/química , Solubilidade , Comprimidos
8.
Rev Med Chir Soc Med Nat Iasi ; 120(3): 720-6, 2016.
Artigo em Inglês | MEDLINE | ID: mdl-30152661

RESUMO

Aim: To develop and validate a fast, robust, isocratic reversed-phase high performance liquid chromatographic method for the determination of bisoprolol in bulk and pharmaceutical formulations. Material and Method: Optimum separation of bisoprolol was achieved using as stationary phase a Zorbax SB-C18 column (100×3 mm; 5µm). The mobile phase was a mixture of phosphate buffer (pH = 3.5) and acetonitrile (70:30) with a flow rate of 1mL/min. The UV detection was performed at 225nm. The temperature of the column and autosampler was 25°C. The specificity was assessed by using metoprolol as internal standard. The method was validated in accordance with the current ICH guidelines in terms of linearity, limit of detection, limit of quantification, precision, accuracy, recovery and system suitability. Results: The retention time for bisoprolol was 1.158 minute. The calibration graph was linear in the concentration range 5-90 µg/mL. The LOD and LOQ of bisoprolol were 1.63 µg/mL and 4.94 µg/mL, respectively. The intra and interday precision of measurements were lower than the accepted criteria (RSD ≤ 2%). The recovery values of HPLC determination of bisoprolol from tablets proved that none of the excipients influenced the results of the analysis. Conclusions: The assay it was found to be accurate, reproducible, sensitive and less time consuming. The proposed method can be successfully applied to quality control studies of pharmaceutical products.


Assuntos
Bisoprolol/análise , Cromatografia Líquida de Alta Pressão/métodos , Preparações Farmacêuticas/análise , Cromatografia de Fase Reversa , Reprodutibilidade dos Testes , Comprimidos
9.
Rev Med Chir Soc Med Nat Iasi ; 119(4): 1161-5, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26793864

RESUMO

AIM: The formulation of sustained release tablets of AMD-HCl using KOLLIDON SR as matrix-forming agent. Chitosan, a natural polysaccharide with superior hydrating and absorbing properties was used in the formulation stage to optimize the release characteristics of those matrix tablets. MATERIAL AND METHODS: Nine formulations of sustained release matrix tablets of AMD x HCl (200 mg/tablet) were prepared through direct compression. The concentrations of matrix forming agents were included as independent variables of a type 2(3) mixed factorial plan in order to develop formulations of AMD-HCl with optimal release characteristics. The dependent variables of that plan were the amount of AMD released from the tablets studied by using in vitro dissolution testing. The test was carried out in the paddle apparatus II for 12 hours in two pH media that were relevant to oral delivery: 2 hours at pH 1.2 and 10 hours at pH 6.8. The released AMD-HCl was quantitatively determined through a validated HPLC method. RESULTS: The increase in KOL concentration leads to a decrease in AMD release rate at both pH values. The use of CHT resulted in a decrease of AMD release only at pH 6.8 in formulations with the lowest concentration of KOL. CONCLUSIONS: The retarding effect on the release of AMD-HCl in the tablets developed in this study was directly proportional to the KOL concentration in the formulation.


Assuntos
Amiodarona/síntese química , Quitosana/síntese química , Preparações de Ação Retardada/síntese química , Excipientes Farmacêuticos/síntese química , Povidona/síntese química , Amiodarona/química , Química Farmacêutica , Quitosana/química , Cromatografia Líquida de Alta Pressão/métodos , Preparações de Ação Retardada/farmacocinética , Concentração de Íons de Hidrogênio , Excipientes Farmacêuticos/química , Povidona/química , Solubilidade , Comprimidos/química
10.
Rev Med Chir Soc Med Nat Iasi ; 119(4): 1199-204, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26793870

RESUMO

AIM: A new spectrophotometric method for the assay of lisinopril using 2,4-dinitrophenol as reagent is described. MATERIAL AND METHODS: The method involved the addition of 2,4-dinitrophenol to lisinopril in methanol followed by absorbance measurement at 400 nm. Experimental conditions that provide wide linear range, maximum sensitivity, selectivity, accuracy and precisions were optimized. RESULTS AND DISCUSSIONS: Beer's law was obeyed in the concentration range 2.0-14.0 µg/mL. Linear regression equation of calibration graph was A = 0.005 + 0.045 x concentration, with a regression coefficient (r) of 0.9995 (n = 8). The limits of detection (LOD) and quantification (LOQ) calculated according to the ICH guidelines were 0.42 and 1.42 µg/mL, respectively. Accuracy and precision of the assays were determined by computing the intra-day and inter-day variations at three different lisinopril concentrations; the intra-day and inter-day RSD was < 1.43% and accuracy was better than 1.72%. CONCLUSIONS: The proposed method is simple, easy to perform, sensitive, linear, precise, accurate and robust.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Lisinopril/química , Espectrofotometria/métodos , 2,4-Dinitrofenol/química , Química Farmacêutica , Indicadores e Reagentes/química , Computação Matemática , Metanol/química , Reprodutibilidade dos Testes
11.
Rev Med Chir Soc Med Nat Iasi ; 119(4): 1189-94, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26793868

RESUMO

AIM: To develop sustained release matrix tablets based on xanthan as highly water-soluble, cost-effective, non-toxic, easily available, and suitable hydrophilic systems. MATERIAL AND METHODS: Xanthan and lignin epoxy-modified resin (LER) mixture were crosslinked using epichlorohydrin as crosslinking agent leading to superabsorbent hydrogels with high swelling rate in aqueous mediums. RESULTS AND CONCLUSIONS: These hydrogels were tested as carries by the loading/delivery behaviour of bisoprolol fumarate in physiological conditions and based on the obtained results these hydrogels may show interest for application in medical and pharmaceutical areas. The amount of drug loaded in polymer networks was found to be ranging between 14.4% and 19.2%. Drug release was retarded and the release mechanism of the active principle was found to depend on matrix composition.


Assuntos
Anti-Hipertensivos/farmacocinética , Bisoprolol/farmacocinética , Portadores de Fármacos/química , Hidrogéis/química , Lignina/química , Polissacarídeos Bacterianos/química , Anti-Hipertensivos/síntese química , Anti-Hipertensivos/química , Bisoprolol/síntese química , Bisoprolol/química , Química Farmacêutica , Preparações de Ação Retardada/química , Liberação Controlada de Fármacos , Técnicas In Vitro
12.
Rev Med Chir Soc Med Nat Iasi ; 119(4): 1195-8, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26793869

RESUMO

AIM: The cooper(II) complex combination of N, N'-disalicylidenemethylenediamine and the Schiff bis base were investigated for anti-inflammatory activity. MATERIAL AND METHODS: In vivo, the anti-inflammatory activity of the metallic complex in comparison with the activity of the Schiff bis base was tested by the method of Winter and co-workers using the Levy technique. RESULTS AND DISCUSSIONS: Our study on the anti-inflammatory activity of a new Schiff bis base and its complex cooper(II) combination showed that the Schiff bis bases exhibited significant anti-inflammatory action in acute experimental inflammation when compared to the control group. The copper cation from the complex combination enhanced the anti-inflammatory effect of the Schiff bis base, the effect being stronger at doses of 10 mg/kg cooper(II) complex. CONCLUSIONS: The Schiff bis base and its cooper(II) complex had an anti-inflammatory effect comparable to that of indomethacin.


Assuntos
Anti-Inflamatórios/síntese química , Anti-Inflamatórios/farmacologia , Cobre/química , Diaminas/síntese química , Diaminas/farmacologia , Bases de Schiff/síntese química , Oligoelementos/química , Anti-Inflamatórios/química , Humanos
13.
Rev Med Chir Soc Med Nat Iasi ; 118(2): 558-63, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-25076731

RESUMO

UNLABELLED: Bisoprolol fumarate is prescribed for the treatment of hypertension and angina pectoris. AIM: The purpose of this study was to develop a simple, sensitive, accurate, and reproducible method for estimation of bisoprolol fumarate in tablets. MATERIAL AND METHODS: The proposed method was based on a yellow colored complex formed with tropaeolin 00, extractable in dichloromethane with maximum absorbance at 412 nm. The method was validated statistically. RESULTS: The linearity domain was observed in the concentration of 5-30 microg/ml. The recovery studies confirmed the accuracy of the proposed method. CONCLUSIONS: The proposed method can be applied for the routine analysis of bisoprolol from formulations.


Assuntos
Anti-Hipertensivos/análise , Bisoprolol/análise , Espectrofotometria/métodos , Comprimidos/análise , Anti-Hipertensivos/química , Compostos Azo/química , Benzenossulfonatos/química , Bisoprolol/química , Corantes/química , Formas de Dosagem , Combinação de Medicamentos , Cloreto de Metileno/química , Reprodutibilidade dos Testes
14.
Rev Med Chir Soc Med Nat Iasi ; 117(2): 520-4, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-24340540

RESUMO

UNLABELLED: Bisoprolol is a drug belonging to beta blockers drugs used primarily for the treatment of cardiovascular diseases. AIM: A spectrophotometric method for quantitative determination of bisoprolol was developed based on the formation of a complex combination between bisoprolol and picric acid. MATERIAL AND METHODS: The complex combination of bisoprolol and picric acid has a maximum absorbance peak at 420 nm. Optimum working conditions were established and the method was validated. RESULTS: The method presented a good linearity in the concentration range 5-120 microg/ml (regression coefficient r2 = 0.9992). The RSD for the precision of the method was 1.74 and for the intermediate precision 1.43, and recovery values ranged between 98.25-101.48%. CONCLUSIONS: The proposed and validated spectrophotometric method for the determination of bisoprolol is simple and cost effective.


Assuntos
Antagonistas de Receptores Adrenérgicos beta 1/análise , Bisoprolol/análise , Indicadores e Reagentes , Picratos , Espectrofotometria/métodos , Antagonistas de Receptores Adrenérgicos beta 1/química , Bisoprolol/química , Reprodutibilidade dos Testes
15.
Rev Med Chir Soc Med Nat Iasi ; 116(4): 1218-22, 2012.
Artigo em Inglês | MEDLINE | ID: mdl-23700915

RESUMO

UNLABELLED: Ramipril is a drug of the angiotensin converting enzyme inhibitor class. AIM: A new molecular absorbance spectrometric method was developed for the assay of ramipril using molybdophosphoric acid in acidic medium. MATERIAL AND METHODS: The reaction product showed a maximum absorbance at 361 nm. The optimum conditions of the reaction were established. The developed method was validated. RESULTS: The method showed a good linearity in the range of 8 - 36 microg/ml (correlation coefficient r = 0.9996). The detection limit (LD) was 0.86microg/ml and the quantification limit (LQ) 2.88 pg/ml. Precision and accuracy were determined (RSD = 1.15%); mean recovery was 98.90% in the 97.13-101.03% concentration range. CONCLUSIONS: The proposed method is simple, easy to perform, sensitive, linear, precise, accurate and robust.


Assuntos
Inibidores da Enzima Conversora de Angiotensina/química , Indicadores e Reagentes/química , Molibdênio/química , Ácidos Fosfóricos/química , Ramipril/química , Espectrofotometria/métodos , Inibidores da Enzima Conversora de Angiotensina/análise , Limite de Detecção , Ramipril/análise , Reprodutibilidade dos Testes
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