Sildenafil citrate (SILC) is a potent phosphodiesterase-5 inhibitor used for erectile dysfunction and pulmonary hypertension. This study shows two simple, fast and alternative analytical methods for SILC determination by non-aqueous titration and by derivative ultraviolet spectrophotometry (DUS) in active pharmaceutical ingredient and/or dosage forms. The quantitation method of SILC active pharmaceutical ingredient by non-aqueous acid-base titration was developed using methanol as solvent and 0.1 mol/L of perchloric acid in acetic acid as titrant. The endpoint was potentiometrically detected. The non-aqueous titration method shows satisfactory repeatability and intermediate precision (RSD 0.70-1.09%). The neutralization reaction occurred in the stoichiometric ratio 1:1 in methanol. The determination of SILC active pharmaceutical ingredient or dosage forms by DUS was developed in the linear range from 10 to 40 µg/mL, in 0.01 mol/L HCl, using the first order zero-peak method at λ 256 nm. The DUS method shows selectivity toward tablets excipients, appropriate linearity (R2 0.9996), trueness (recovery range 98.86-99.30%), repeatability and intermediate precision in three concentration levels (RSD 1.17-1.28%; 1.29-1.71%, respectively). Therefore, the methods developed are excellent alternatives to sophisticated instrumental methods and can be easily applied in any pharmaceutical laboratory routine due to simple and fast executions.

Stryphnodendron adstringens (Mart.) Coville (barbatimão) é uma árvore da família Fabaceae encontrada no cerrado do sudeste do Brasil. As cascas do caule das espécies são tradicionalmente utilizadas como agente antiinflamatório e antisséptico para o tratamento de diarreia e leucorreia, bem como para promover a cicatrização de feridas, devido à presença de proantocianidinas. Estas substâncias obtidas a partir do extracto etanólico (EE) de cascas do caule de S. adstringens foram avaliadas por cromatografia líquida de alta eficiência de fase reversa. As substâncias identificadas foram ácido gálico, catequina, galocatequina (GC), epigalocatequina e galato de epigalocatequina (EGCG). Os marcadores selecionados, GC e EGCG, foram utilizados simultaneamente para validação cromatográfica (intervalo de linearidade 30-330 ng, equivalente a 3-33 µg/mL, r>0,998). O método mostrou precisão (intra-dia DPR 1,72% para GC; 1,16% para EGCG; inter-dia DPR 1,74%-2,60% para ambos os marcadores), exatidão, robustez e seletividade. Os limites de detecção e de quantificação de 0,29 µg/mL e 0,89 µg/mL para a GC, e 0,88 ng/mL e 2,67 µg/mL para EGCG, respectivamente. Outra espécie (S. obovatum) avaliada, mostrou valores médios 12,2 µg/mL de GC (equivalente a 1,22% p/p) e 14,2 µg/mL de EGCG (equivalente a 1,42% p/p) encontrados no EE. Os resultados quantitativos comparam-se aos de S. adstringens e mostram que tais marcadores estão presentes em ambas as espécies.

Stryphnodendron adstringens (Mart.) Coville (barbatimão) is a tree belonging to the Fabaceae family, and it is commonly found in the southeastern Brazilian cerrado. The stem bark of this tree is traditionally used as an anti-inflammatory and antiseptic agent to treat leucorrhea and diarrhea, as well as to promote wound healing (owing to the presence of proanthocyanidins). Proanthocyanidins were obtained from the ethanolic extract of S. adstringens stem bark and assessed by reversed phase-high performance liquid chromatography with an ultraviolet/diode array detector. The identified compounds included gallic acid, catechin, gallocatechin (GC), epigallocatechin, and epigallocatechin gallate (EGCG). The selected markers, GC and EGCG, were simultaneously used for chromatographic validation (linearity range: 30-330 ng, equivalent to 3-33 µg/mL; r>0.998). The method showed precision (intra-day relative standard deviation [RSD]: 1.72% for GC; 1.16% for EGCG; inter-day RSD: 1.74%-2.60% for both markers), accuracy, robustness, and selectivity. The limits of detection and quantitation were 0.29 µg/ml and 0.89 µg/ml for GC, and 0.88 µg/mL and 2.67 µg/mL for EGCG, respectively. In addition, S. obovatum was evaluated and showed an average of 12.2 µg/mL for GC (equivalent to 1.22% w/w) and 14.2 µg/mL for EGCG (equivalent to 1.42% w/w) in the ethanolic extract. The quantitative results were compared to those obtained for S. adstringens, which showed that the markers are present in both species.

Commonly used HPLC acetonitrile solvent has been through a worldwide shortage with a cost increase in 2008 and 2009. In order to get around this situation, a method by RP-HPLC employing methanol and aqueous acid mobile phase was developed and validated to evaluate simvastatin. The quality control assay and dissolution studies of this lipid-lowering drug were performed in diluents methanol and 0.01 M phosphate buffer with 0.5% SDS, pH 7, respectively. Dissolution test aliquots did not go through sample treatment, as described in USP SIM tablets monograph by ultraviolet spectrophotometry. The proposed method is fast, simple, feasible and robust.

The bioassay, first order derivative UV spectrophotometry and chromatographic methods for assaying fluconazole capsules were compared. They have shown great advantages over the earlier published methods. Using the first order derivative, the UV spectrophotometry method does not suffer interference of excipients. Validation parameters such as linearity, precision, accuracy, limit of detection and limit of quantitation were determined. All methods were linear and reliable within acceptable limits for antibiotic pharmaceutical preparations being accurate, precise and reproducible. The application of each method as a routine analysis should be investigated considering cost, simplicity, equipment, solvents, speed, and application to large or small workloads.

No Brasil, a sinvastatina está comercialmente disponível na forma de comprimidos e cápsulas manipuladas. Poucos relatos estão disponíveis sobre a qualidade e, consequentemente, a eficácia dessas cápsulas. A qualidade de 30 lotes de sinvastatina 20 mg cápsulas do mercado foi avaliada através da determinação de peso, uniformidade de conteúdo, desintegração (Farmacopéia Brasileira), doseamento e teste de dissolução (monografia comprimidos USP32). Método por CLAE foi desenvolvido para o doseamento, uniformidade de conteúdo e teste de dissolução; além disso, especificações foram estabelecidas. Dos 30 lotes avaliados, 29 apresentaram desintegração da cápsula até 45 min e a variação do peso individual foi ± 10% ou ± 7,5% em relação ao peso médio, se < ou > 300 mg, respectivamente. Apenas 27 lotes preencheram os critérios do teste de dissolução com valores > 80% da quantidade rotulada, em 45 min, 21 lotes apresentaram conteúdo de sinvastatina entre 90,0-110,0% do valor rotulado e 19 lotes apresentaram pelo menos 9 em 10 cápsulas, com valores de uniformidade de conteúdo entre 85,0 -115,0% da quantidade rotulada com RSD < 6,0%. Apenas 14 de todos os lotes (30) atenderam completamente os padrões de qualidade farmacopéicos. O estabelecimento das condições para os testes e de especificações para os parâmetros das cápsulas de sinvastatina mostrou que houve diferenças relevantes na qualidade farmacopeica entre os lotes das cápsulas manipuladas por distintas farmácias. A eficácia do tratamento hipercolesterolêmico poderia estar comprometida para 53,33% dos produtos testados.

Simvastatin is commercially available as tablets and compounded capsules in Brazil. Very few reports regarding these capsules' quality, and consequently their efficacy, are available. The pharmaceutical quality of 30 batches of 20 mg simvastatin capsules from the market was evaluated by weight determination, content uniformity, disintegration (Brazilian Pharmacopeia), assay and dissolution test (USP32 tablet monograph). A HPLC method was developed for assay, content uniformity and dissolution test, and specifications were also established. Out of the 30 batches evaluated, 29 showed capsule disintegration within 45 min and individual weight variation was within ±10% or ±7.5% relative to average weight, for < or > 300 mg, respectively. Only 27 batches met dissolution test criteria with values >80% of the labeled amount in 45 min; 21 batches showed simvastatin content between 90.0-110.0% of the labeled amount and 19 batches had at least 9 out of 10 capsules with content uniformity values between 85.0-115.0% of the labeled amount with RSD<6.0%. Only 14 of all (30) batches fully met pharmacopeial quality standards. The establishment of test conditions and specification parameters for simvastatin capsules showed that there are relevant pharmacopeial quality differences between batches compounded by different pharmacies. For 53.33% of the tested products hypercholesterolemic treatment efficacy may be compromised.

Thermogravimetry (TG) and differential scanning calorimetry (DSC) are used in pharmaceutical studies for drugs characterization, purity, formulations compatibility, polymorphism identification, stability evaluation, and thermal decomposition of drugs and pharmaceutical formulations. Simvastatin showed fusion at 138.5 ºC and thermal stability up to 248 ºC. Simvastatin was incompatible with preservative excipient butylhydroxyanisole (BHA) performing a process of crystal amorphization. The drug showed morphological polymorphism, where it has the same unit cell but with different crystal habits according to the recrystallization solvent.

A glibenclamida (GLIB) é um fármaco de segunda geração, administrado por via oral na forma de comprimidos, utilizado para o tratamento de Diabetes mellitus. GLIB possui baixa solubilidade aquosa, o que pode levar a uma baixa liberação a partir de formas farmacêuticas sólidas no teste de dissolução e, portanto, a variabilidades no tratamento. Neste estudo, avaliam-se as características da matéria-prima GLIB, que podem influenciar o perfil de dissolução, e conseqüentemente, a biodisponibilidade, por meio de técnicas tais como, adsorção de nitrogênio, difração de raio laser, análise térmica, espectroscopia por IV/UV e difração de raios X.

Glibenclamide (GLIB) or glyburide, a second-generation hypoglycemic agent is orally used in the form of tablets for the treatment of diabetes mellitus. Bulk GLIB has a low aqueous solubility and it may yield low drug release in the dissolution test, causing variabilility in the treatment. This work evaluates the bulk GLIB features, which may influence drug release profile, hence, bioavailability, by means of techniques such as nitrogen sorption analysis, laser diffraction, thermal analysis, IV/UV spectroscopy and X-ray analysis.

This paper describes the development and validation of an UV-Visible spectrophotometric method for quantitation of genistein and genistin in soy dry extracts, after reaction with aluminum chloride. The method showed to be linear (r²= 0.9999), precise (R.S.D. < 2%), accurate (recovery of 101.56%) and robust. Seven samples of soy dry extracts were analyzed by the spectrophotometric validated method and by RP-HPLC. Genistein concentrations determined by spectrophotometry (0.63% - 16.05%) were slightly higher than values obtained by HPLC analysis (0.40% - 12.79%); however, the results of both methods showed a strong correlation.

A utilização de produtos naturais e suplementos contendo extratos secos de isoflavonas aumentou na última década, devido, principalmente, aos efeitos benéficos atribuídos a estes compostos no alívio dos sintomas da menopausa. Genisteína, daidzeína e gliciteína são as agliconas mais abundantes nos extratos de soja, ocorrendo também como glicosídeos. Tendo em vista seus usos, não existe ainda na literatura uma definição da quantidade mínima de cada uma das agliconas que os extratos ou cápsulas de isoflavonas devem ter, e também não existe um método oficial para o controle de qualidade dos mesmos. O presente trabalho apresenta um método por CCD para análise qualitativa das três agliconas e de seus glicosídeos em extratos e cápsulas de isoflavonas, antes e após hidrólise ácida. A análise quantitativa das cápsulas de isoflavonas, realizada por cromatografia líquida de alta eficiência (CLAE), revelou grandes variações nos teores das três agliconas, após hidrólise ácida. Os teores variaram da seguinte forma, nos 18 lotes de cápsulas avaliados: daidzeína (13,34 a 76,20 mg/cápsula), genisteína (0,61 a 27,18 mg/cápsula) e gliciteína (0,49 a 8,80 mg/cápsula).

The use of herbal products and supplements based on isoflavone dry extracts has increased considerably in the last decade, mainly due to beneficial effects to relief of the menopausal symptoms credited to those compounds. Genistein, daidzein and glycitein are the most abundant isoflavone aglycones found in soy extract, where they also occur as glycosides. Concerning their uses, there is neither standardization regarding the minimum content of each aglycone in the extracts or capsules, nor an official method to the quality control of these products. The present work presents a TLC method for qualitative analysis of the three aglycones and their glycosides in extracts and capsules of isoflavones, before and after acid hydrolysis. The quantitative analysis of the isoflavone capsules, carried out by high performance liquid chromatography (HPLC), showed high variation in the content of the three aglycones, after acid hydrolysis. The contents varied in the following way, in the 18 batches of evaluated capsules: daidzein (13.34 to 76.20 mg/capsule), genistein (0.61 to 27.18 mg/capsule) and glycitein (0.49 to 8.80 mg/capsule).

A glibenclamida (GLIB) ou gliburida, é um hipoglicemiante oral de segunda geração, da classe das sulfoniluréias, usado sob a forma de comprimidos para tratamento do diabetes mellitus. Variações no tratamento podem ocorrer, devido à baixa solubilidade do fármaco em comprimidos. A comparação de várias formulações de comprimidos piloto com comprimidos do medicamento referência (Daonil®, glibenclamida 5 mg comprimidos, Aventis Pharma Ltda.) foi avaliada por meio do desenvolvimento de um teste de dissolução sem adição de solventes orgânicos ou tensoativos no meio, que mostrou ser discriminativo para as diferentes formulações farmacêuticas propostas. A quantificação de GLIB foi realizada por meio de cromatografia líquida de alta eficiência em fase reversa (CLAE-FR), método previamente validado. A partir de vários ensaios de perfil de dissolução testados comparativamente àquele de comprimidos do medicamento referência, verificou-se o potencial de determinada formulação proposta (f1 4,04 and f2 69,35) como candidata a medicamento genérico no mercado brasileiro.

Glibenclamide (GLIB) or glyburide, a second-generation hypoglycemic agent is used per oral as tablets for the treatment of diabetes mellitus. Much variabilility in the treatment may occur because of the low drug aqueous solubility in tablets dosage forms. This work reports the comparison of several pilot formulation batches with the commercial reference drug dosage form (Daonil®, glibenclamide 5 mg per tablet, Aventis Pharma Ltda.). A feasible dissolution test, developed with no use of organic solvents or surfactants in the medium, showed to be discriminative regarding to different formulations tested. GLIB quantitation was performed by a previously validated reverse-phase high performance liquid chromatography (RP-HPLC). Among several dissolution profiles compared with that of a commercial reference, a potential for a generic candidate was evident (f1 4.04 and f2 69.35) for a proposed solid dosage formulation in the Brazilian market.

A glibenclamida (GLIB) ou gliburida, agente hipoglicemiante oral de segunda geração, da classe das sulfoniluréias, é usada sob a forma de comprimidos para controle do diabetes mellitus. Possui baixa solubilidade aquosa, podendo proporcionar baixa liberação no teste de dissolução de comprimidos e acarretar variabilidades no tratamento. A solução metanólica de GLIB apresenta máximos de absorção em lambda 210 nm, 227,5 nm e 300 nm na região ultravioleta (UV). Após liberaçao de comprimidos, a sua determinação espectrofotométrica na região UV é dificultada devido à baixa concentração proporcionada após o teste de dissolução (comprimidos GLIB 5 mg, volume de meio 900 mL, 0,56 mg%) e à baixa absortividade em comprimento de onda característico, lambda 300 nm. Por estas razões, até hoje, não existe um método de análise proposto para o teste de dissolução em farmacopéias nacional ou estrangeiras para monografia de glibenclamida comprimidos. A falta de uniformidade nestes procedimentos onera a execução de testes de dissolução para verificação da equivalência farmacêutica de especialidades candidatas a genéricos. Este trabalho propõe a determinação espectrofotométrica de GLIB por derivada de primeira e segunda ordens (máximos lambda 238 nm e 218 nm, respectivamente, em tampão fosfato 0,1 mol L-1), utilizando comprimidos referência e teste contendo 5 mg de fármaco por dose unitária.

Glibenclamide (GLIB) or glyburide, a second-generation oral hypoglycemic drug, is used in the tablet form for the treatment of diabetes mellitus. Because of the low aqueous solubility of this sulfonylurea, a low drug release in the dissolution test may occur, hence, causing variabilility in the treatment. GLIB methanolic solution shows UV absorption maxima in lambda 210 nm, 227.5 nm and 300 nm. After released from tablets in the dissolution test, its spectrophotometric determination is difficult due to the low drug concentration in solution (5 mg GLIB tablets, medium volume 900 mL, 0.56 mg%). In addition, it presents a low absorption in the characteristic wavelength of lambda 300 nm. Up to date, there is no method recommendation for GLIB determination in tablet monographs in many of national or foreign official compendia. For this reason, the dissolution test performance lacks uniformity by official recommended procedures, to prove pharmaceutical equivalence to the reference drug, for generic candidates. GLIB spectrophotometric determination is investigated by first and second derivative orders (peaks at lambda 238 nm and 218 nm, respectively in 0.1 mol L-1 phosphate buffer solution) using reference and test tablets containing 5 mg of GLIB per unit dose.

HEMA/MMA/EDMA (2-hydroxyethyl methacrylate/methyl methacrylate/ethyleneglycol methacrylate) copolymer beads have been synthesized for use in aqueous SEC. This porous chromatographic support consisted of a large average particle size (250 µm) and contained macropores with a median pore size of approximately 880 Å. The material was packed in glass and stainless columns to assess their chromatographic performance. The packed columns were calibrated using narrow molecular weight (MW) distribution standards (dextran) and exhibited a range of molecular weight separation between 40,000 and 2,000,000 daltons. The packing material showed the ability to separate large molecules through the size exclusion mechanism.

A sacarina, adoçante sintético constituinte de várias preparações farmacêuticas e cosméticas, foi analisada de forma qualitativa e quantitativa na presença de substâncias interferentes como princípios ativos e excipientes das formulações. Utilizou-se a espectrofotometria derivada no ultravioleta, por meio da segunda e da quarta ordens de diferenciação. Os resultados obtidos na padronização do método foram satisfatórios e mostraram precisão no intervalo de 0,53%-0,72%, e linearidade entre 0,99980,9999. O teste de recuperação, aplicado na amostra gel dental situou entre 97,80% e 104,95%, para a segunda ordem, e entre 98,04% e 101,32%, para a quarta ordem de diferenciação, respectivamente, empregando os métodos zero-pico (ZP) and pico-pico (PP). A amostra suspensão oral mostrou valores entre 97,35% e 104,72%, para a segunda ordem, e valores entre 95,94% e 104,41%, para a quarta ordem de diferenciação, respectivamente, empregando os métodos zero-pico (ZP) and pico-pico (PP). O método proposto mostrou ser preciso, simples e exato.

Saccharin, a synthetic sweetener constituent of several pharmaceutical and cosmetic preparations, is analyzed qualitatively and quantitatively in the presence of interferences like active ingredients and excipients. A derivative ultraviolet spectrophotometric method employing the second and the fourth orders was used. The calibration data obtained were satisfactory, with a relative precision range of 0.53%-0.72%, and linearity between 0.9998-0.9999. The recovery test results for the toothgel sample ranged between 97.80% and 104.95% in the second order of derivative and between 98.04% and 101.32% in the fourth derivative, respectively, using zero-peak (ZP) and peak-peak (PP) methods. The suspension sample showed values between 97.35% and 104.72% in the second derivative and between 95.94% to 104.41% in the fourth derivative, respectively, employing the zero-peak (ZP) and peak-peak (PP) methods. The proposed method showed precision, accuracy and simplicity.