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Ketoprofen (KTP) is an Active Pharmaceutical Ingredient (API) that has low solubility in aqueous solvents. The use of KTP salts has attracted attention due to its improvements in terms of solubility, tolerability, higher rate and extent of absorption, and faster onset of the therapeutic effect. In this work, a crystalline KTP sodium salt (coded as KTP-Na) was successfully obtained and widely characterized by X-ray powder diffraction (XRD), Fourier transform infrared spectroscopy (FTIR), differential scanning calorimetry (DSC), thermogravimetric analysis (TGA), solubility and accelerated stability studies. XRD results showed that KTP-Na is not yet reported in the literature. Moreover, FTIR, DSC and TGA were useful for differentiation of KTP-Na from the KTP commercialized form (coded as KTP-R1). The solubility of KTP-Na in water was about 80 times greater than the KTP-R1. However, KTP-Na showed lower physical stability in storage conditions at 40 ± 2°C/ 75% ± 5% RH when compared to KTP-R1, which was shown to be related to a high hygroscopicity of KTP-Na. Therefore, due to its higher solubility, KTP-Na may be a viable alternative for use in solid dosage forms. However, the presence of moisture must be strictly controlled to avoid water absorption and consequent amorphization.

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Corticosteroids are a class of hormones released by the adrenal cortex, which includes glucocorticoids and mineralocorticoids. Glucocorticoids have an important role in the metabolism of carbohydrates, proteins and calcium and effective anti-inflammatory and immunosuppressive activity. Due to their intense immunomodulatory and anti-inflammatory activity, glucocorticoids are used in the treatment of various inflammatory, malignant, allergic conditions such as rhinitis, asthma, dermatological, rheumatic, ophthalmic and neurological diseases, as well as after organ transplants. They are the most widely prescribed drugs in the world. The objective of this review is to provide an overview of the analytical methods in pharmaceutical matrices for determination of corticosteroids. In this study, the predominance of liquid chromatography methods for the analysis of corticosteroids from pharmaceutical products is evident for both liquid and semisolid dosage forms as well as for solids. The same can be said for topical, oral and parenteral formulations. Methods such as spectrophotometry are also used, but given the advantages of chromatographic methods such as better selectivity and sensitivity, they have become the choice for analysis of these drugs, however, most methods still do not meet the credentials of "green chemistry."

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We propose to evaluate the dissolution properties of rosuvastatin calcium (ROSC) capsules in different media to characterize the discriminatory power of the assay method. Dissolution assays were performed in media with different pH, and including the surfactant sodium dodecyl sulfate (SDS). Several immediate-release formulations were manufactured using the commercial raw material characterized as amorphous solid. The hydrophobic adjutant magnesium stearate was employed in some formulations due to its negative effect in the wettability and dissolution efficacy of solid dosages. These formulations showed the lower dissolution efficacy values in media without surfactant; however, when SDS was added to the medium, the dissolution efficacy increased, and the discriminatory power was lost. In spite of micellar solubilization does not increase the ROSC solubility, it modifies the discriminatory power of the assay method, increasing the wettability of the powder mixtures. The crystalline form M of ROSC was recrystallized in our laboratory, and it showed lower solubility in water than amorphous solid. However, its dissolution properties were not influenced by SDS. These results are important to develop dissolution assays for other hydrophilic drugs with increased water solubility, once that dissolution media with surfactants increase the wettability of the formulations, leading to an overrated dissolution rate.

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Glimepiride (GLIM) is used as an oral antihyperglycemic agent for treatment of type 2 diabetes. The drug presents two polymorphic forms (GLIM form I and GLIM form II) described in the literature, and according to in vitro data, GLIM form II is about 3.5 times more soluble and releases 2 times the drug amount than GLIM form I in the physiological pH range. Considering the literature in vitro data and that the diabetes treatment demands glycemic control, avoiding abrupt fluctuations in the blood glucose levels, this work aimed to study the impact of GLIM polymorphism in the in vivo performance of GLIM solid oral dosages. For this, hard gelatin capsules with GLIM form I or II were prepared and orally administered in rats. After that, pharmacokinetic studies were performed by sampling animal blood at different times, and biochemical parameters (pharmacodynamic), such as glucose and insulin, were also evaluated. Our results showed that the in vitro data corroborate with our in vivo assays. GLIM form II provided higher plasma concentration of drug than form I (at baseline up to approximately 200 min after oral administration) and, consequently, increased insulin release and reduced levels of glucose, showing good correlation between pharmacokinetic and pharmacodynamics assays. Thus, this study demonstrated that GLIM polymorphs in oral dosages might alter the drug efficacy, which may expose the patients to risks, such as hypoglycemia.

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Rosuvastatin calcium (ROS), ( Figure 1 ) belongs to the "statins" group, which is the 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitor. This drug is indicated for dyslipidemias treatment and can help to decrease the level of "bad cholesterol" and can consequently reduce the development of atherosclerosis and the risk of heart diseases. ROS was developed by Astra-Zeneca and it was approved in 2003 by the FDA in the United States. In 2015, under the trade name Crestor®, it was the fourth largest selling drug in the United States with sales above $5 billion. This study presents a literature review of analytical methods for the quantification of ROS in pharmaceutical preparations and biological fluids. The major analytical methods described in this study for ROS were spectrophotometry, high-performance liquid chromatography (HPLC) coupled to ultraviolet (UV) detection, and tandem mass spectrometry (LC-MS/MS).

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ABSTRACT Spironolactone (SPR) is a steroidal drug administered as a potassium-sparing diuretic for high blood pressure treatment. The drug shows incomplete gastrointestinal absorption due to its poor aqueous solubility. The physicochemical properties of SPR in crystal forms I and II suggest that differences in their aqueous solubility may lead to a lack of bioequivalence between solid-state formulations. In this study, SPR polymorphs in five batches of active pharmaceutical ingredients (APIs) from three manufacturers were characterized using powder X-ray diffraction, infrared spectroscopy, thermal analysis, and solubility measurements. SPR tablets (50 mg) were manufactured in our laboratory using API in pure form II, and API in form II contaminated with form I, which was found in a commercial batch. Physicochemical quality evaluations of the manufactured tablets, along with five SPR tablets marketed in Brazil, were performed, and results indicated differences in their dissolution profiles. In the manufactured tablets, differences were associated with the increased solubility of API in form II contaminated with form I compared to API in pure form II. In the marketed SPR tablets, the formulation composition demonstrated an important role in the dissolution rate of the drug, leading to lack of pharmaceutical equivalence among the drug products.

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Orbifloxacin (ORBI) is a widely used antimicrobial drug of the fluoroquinolone class. In the official pharmaceutical compendia the existence of polymorphism in this active pharmaceutical ingredient (API) is reported. No crystal structure has been reported for this API and as described in the literature, its solubility is very controversial. Considering that different solid forms of the same API may have different physicochemical properties, these different solubilities may have resulted from analyses inadvertently carried out on different polymorphs. The solubility is the most critical property because it can affect the bioavailability and may compromise the quality of a drug product. The crystalline structure of ORBI determined by SCXRD is reported here for the first time. The structural analysis reveals that the ORBI molecule is zwitterionic and hemihydrated. ORBI hemihydrated form was characterized by the following techniques: TG/DTA, FTIR-ATR, and PXRD. A second crystalline ORBI form is also reported: the ORBI anhydrous form was obtained by heating the hemihydrate. These ORBI solid forms were isomorphous, since no significant change in unit cell and space group symmetry were observed. The solid-state phase transformation between these forms is discussed and the equilibrium solubility data were examined in order to check the impact of the differences observed in their crystalline structures.

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O setor magistral promove o acesso da população a medicamentos essenciais e fornece produtos individualizados. Entretanto, a qualidade dos medicamentos manipulados no Brasil é frequentemente questionada, apesar de existirem poucos dados científicos abrangentes sobre a qualidade destes produtos. O objetivo deste trabalho foi fazer um levantamento de análises físico-químicas e microbiológicas realizadas em 2347 amostras de produtos manipulados entre janeiro de 2010 e dezembro de 2011, em 117 diferentes farmácias de 49 municípios brasileiros. Os municípios selecionados foram todos aqueles que possuem farmácias conveniadas ao laboratório que realizou o estudo. Das amostras analisadas, 21,4% apresentaram não conformidades físico-químicas, sendo que vários hormônios e antibióticos foram reprovados. Com relação aos ensaios microbiológicos, 0,96% das bases galênicas e 0,20% dos produtos acabados analisados apresentaram não conformidades, sendo identificados micro-organismos patogênicos nestes produtos. Apesar das exigências cada vez maiores das autoridades sanitárias em relação a produtos manipulados, com base nestes resultados, nós chamamos atenção quanto à qualidade destes produtos.

Compounding pharmacies allow the population access to essential medications and individualized products. Despite the insufficient comprehensive scientific data on this issue, the quality of medications compounded in Brazil is often questioned. the aim of the present study was to evaluate the physicochemical and microbiological quality of 2347 samples of medications compounded between January 2010 and December 2011 at 117 different pharmacies located in 49 Brazilian cities. All cities with pharmacies affiliated to the laboratory that undertook the study were selected. A total of 21.4% of the samples analyzed exhibited physicochemical non-compliance and a number of hormones and antibiotics were rejected in the tests. Regarding microbiological tests, 0.96% of the galenic bases and 0.20% of the finished products analyzed exhibited non-compliance. Moreover, pathogens were identified in these products. Despite the demands of health authorities for higher standards regarding compounded medications, the present findings call the quality of such products into question.

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The aim of this study was to develop and validate a method for evaluating the release and skin permeation from transdermal nicotine patches using the vertical diffusion cell (VDC). The VDC is an experimental apparatus employed in research, development, and the pharmaceutical field because it can simulate conditions closest to those established in clinical trials. Two transdermal nicotine delivery systems marketed in Brazil to release 14 mg over 24 hours were evaluated. Release studies were carried out using a regenerated cellulose dialysis membrane and permeation studies were carried out using excised porcine ear skin. The results indicated that nicotine release from both evaluated patches follows Higuchi's release kinetics, while skin permeation studies indicated zero-order release kinetics. Nicotine release rates were different between both evaluated patches, but drug permeation rates were not significantly different. According to validation studies, the method was appropriate for evaluating in vitro performance of nicotine patches. The proposed method can be applied to in vitro comparative studies between different commercial nicotine patches and may be used as an auxiliary tool in the design of new transdermal nicotine delivery systems.

O objetivo deste trabalho foi o desenvolvimento e a validação de metodologia empregando a célula de difusão vertical para avaliação da liberação e permeação cutânea in vitro de nicotina a partir de adesivos transdérmicos. A célula de difusão vertical é considerada um aparato experimental importante em pesquisa e desenvolvimento e pode simular condições in vitro próximas aquelas observadas em ensaios clínicos. Neste trabalho foram avaliados dois dispositivos transdérmicos comercializados no Brasil para liberação controlada de 14 mg de nicotina em um período de 24 horas. Realizaram-se ensaios de liberação, usando membranas de diálise de celulose regenerada, e estudos de permeação cutânea, usando pele de orelha de porcos. Os resultados indicaram que a liberação da nicotina em ambos os dispositivos transdérmicos avaliados seguiu a cinética de Higuchi, enquanto que a permeação cutânea seguiu cinética de ordem zero. As velocidades de liberação foram diferentes para os dispositivos comerciais avaliados, entretanto não foram encontradas diferenças significativas para as velocidades de permeação cutânea. Conforme os estudos de validação, a metodologia mostrou-se apropriada para a avaliação in vitro da liberação e permeação cutânea a partir de adesivos transdérmicos de nicotina. O método proposto foi aplicado em estudos comparativos in vitro entre adesivos transdérmicos comerciais contendo nicotina. Deste modo, o método também pôde ser considerado como ferramenta útil que poderia ser aplicada durante o desenvolvimento de novas formulações transdérmicas para liberação de nicotina.

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Glimepiride is an oral antidiabetic drug in the sulfonylurea class, which is widely used in treatment of Type 2 diabetes and it is currently available in more than 60 countries worldwide. As a result of the importance of this oral hypoglycemic agent in the treatment of noninsulin-dependent diabetes mellitus, this work aims to compile the published analytical methods reported so far in the literature for determination of glimepiride in biologic samples and pharmaceutical formulations. Techniques like high-performance liquid chromatography with ultraviolet, array-diode, mass spectroscopy, evaporative light scattering and charged aerosol detections, liquid chromatography-atmospheric pressure chemical ionization-mass spectrometry, liquid chromatography-electrospray ionization-tandem mass spectrometry, semimicrobore high-performance liquid chromatography with column-switching, micellar electrokinetic chromatography, high-performance thin layer chromatography, polarography, and spectrophotometry have been used for analysis, from which it can be seen that high-performance liquid chromatography methods have been used most extensively.

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Losartan potassium is an antihypertensive non-peptide agent, which exerts its action by specific blockade of angiotensin II receptors. The aim of the present study was the validation and application of analytical methods for the quality control of losartan potassium 50 mg in pharmaceutical capsules, using direct and first-derivative UV spectrophotometry. Based on losartan potassium spectrophotometric characteristics, a signal at 205 nm of the zero-order spectrum and a signal at 234 nm of the first-derivative spectrum, were found adequate for quantification. The results were used to compare these instrumental techniques. The linearity between the signals and concentrations of losartan potassium in the ranges of 3.0-7.0 mg L-1 and 6.0-14.0 mg L-1 for direct and first-derivative spectrophotometry in aqueous solutions, respectively, presented a correlation coefficient (r) of 0.9999 in both cases. The methods were applied for losartan potassium in capsule dosage obtained from local pharmacies, and were shown to be efficient, easy to apply and low cost. These methods do not use polluting reagents and require relatively inexpensive equipment.

O losartano potássico é um agente anti-hipertensivo não peptídico, que exerce sua ação por bloqueio específico dos receptores da angiotensina II. Este trabalho propôs a validação e aplicação de métodos analíticos orientados ao controle de qualidade de losartano potássico 50 mg na forma farmacêutica cápsula, utilizando a espectrofotometria direta e derivada de primeira ordem na região do UV. Baseado nas características espectrofotométricas de losartano potássico, um sinal a 205 nm do espectro de ordem zero e um sinal a 234 nm do espectro de primeira derivada foram adequados para a quantificação. Os resultados foram usados para comparar essas duas técnicas instrumentais. O coeficiente de correlação entre as respostas e as concentrações de losartano potássico na faixa de 3,0-7,0 mg L-1 e 6,0-14,0 mg L-1 para espectrofotometria direta e derivada de primeira ordem em solução aquosa, respectivamente, foi de (r) of 0,9999 para ambos os casos. Os métodos foram aplicados para quantificação de losartano potássico em cápsulas obtidas de farmácias de manipulação locais e demonstraram ser eficientes, fáceis de aplicar e de baixo custo. Além disso, não necesitam de reagentes poluentes e requerem equipamentos economicamente viáveis.

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This paper describes the optimization and validation of an analytical methodology for the determination of losartan potassium in capsules by HPLC using 2(5-1) fractional factorial and Doehlert designs. This multivariate approach allows a considerable improvement in chromatographic performance using fewer experiments, without additional cost for columns or other equipment. The HPLC method utilized potassium phosphate buffer (pH 6.2; 58 mmol L(-1))-acetonitrile (65:35, v/v) as the mobile phase, pumped at a flow rate of 1.0 mL min(-1). An octylsilane column (100 mm x 4.6mm i.d., 5 microm) maintained at 35 degrees C was used as the stationary phase. UV detection was performed at 254 nm. The method was validated according to the ICH guidelines, showing accuracy, precision (intra-day relative standard deviation (R.S.D.) and inter-day R.S.D values <2.0%), selectivity, robustness and linearity (r=0.9998) over a concentration range from 30 to 70 mg L(-1) of losartan potassium. The limits of detection and quantification were 0.114 and 0.420 mg L(-1), respectively. The validated method may be used to quantify losartan potassium in capsules and to determine the stability of this drug.

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Meloxicam is a broadly used drug in the therapeutics for the osteoarthritis and rheumatoid arthritis treatments in adults, and it is available in the Brazilian market, as tablet and capsule pharmaceutical forms. The present work aimed to establish conditions for accomplishment of the dissolution test of 15 mg meloxicam tablets (A and B test products), compared with the reference product, since there is no monograph about dissolution assays for meloxicam in official summaries. To optimize the conditions several parameters were tested and, according to obtained results, the use of pH 7.5 phosphate buffer (900mL, at 37 ± 0.5ºC) as dissolution medium, paddle method (apparatus 2), stirring speed of the dissolution medium at 100 rpm and collect time of 60 minutes were considered satisfactory. The samples were quantified by UV spectrophotometric method at 362 nm. The products presented kinetics of first-order. Dissolution efficiency values were of 83.25, 83.73 and 88.10 percent for the A, B and reference products, respectively. Factors f1 and f2 were calculated and similarity of the tested medicines was demonstrated. The dissolution test was validated presenting selectivity, linearity, precision and accuracy within of the acceptance criteria.

O meloxicam é fármaco amplamente utilizado na terapêutica para o tratamento de osteoartrite e artrite reumatóide em adultos, e encontra-se disponível no mercado brasileiro, sob as formas farmacêuticas comprimido e cápsula. O presente trabalho objetivou estabelecer condições para realização do teste de dissolução de meloxicam 15 mg na forma farmacêutica comprimido (medicamentos-teste A e B), comparado com o medicamento de referência, visto que não há monografia para o ensaio de dissolução com meloxicam em compêndios oficiais. Para otimização das condições, diversos parâmetros foram testados e de acordo com os resultados obtidos, a utilização de tampão fosfato pH 7,5 (900mL, a 37 ± 0,5 ºC) como meio de dissolução, aparato 2 (pá), velocidade de agitação do meio de dissolução de 100 rpm e tempo de coleta em 60 minutos, foram considerados satisfatórios. As amostras foram quantificadas por espectrofotometria na região do ultravioleta, a 362 nm. Os produtos apresentaram cinética de primeira ordem. Para a eficiência de dissolução encontraram-se valores de 83,25, 83,73 e 88,10 por cento para os medicamentos-teste A e B e referência, respectivamente. Os fatores f1 e f2 foram calculados, demonstrando haver similaridade entre os medicamentos avaliados. O ensaio de dissolução foi validado apresentando seletividade, linearidade, precisão e exatidão dentro dos critérios de aceitação.

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O fluconazol, derivado triazólico, apresenta atividade antifúngica sendo indicado no tratamento de grande variedade de infecções fúngicas. Este trabalho foi desenvolvido com o objetivo de estabelecer parâmetros de controle de qualidade para a matéria prima de fluconazol e forma farmacêutica cápsula, subsidiando a elaboração da monografia para a Farmacopéia Brasileira. A matéria-prima do fluconazol pode ser caracterizada pelos seguintes testes: aspecto, solubilidade e faixa de fusão. As impurezas do fluconazol podem ser detectadas por ensaio-limite de cloreto, sulfato, ferro, metais pesados, perda por dessecação e cinzas sulfatadas...

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Este trabalho foi desenvolvido para análise da oxamniquina matéria-prima e para a elaboração de metodologias no controle de qualidade de suas especialidades farmacêuticas, supensão e cápsulas, especialmente em atenção à introdução da classe dos genéricos e possíveis similares. Foram realizados testes de caracterização, identificação e doseamento tanto para matéria-prima como para as formas faramcêuticas. Os resultados dos testes de caracterização mostraram-se estar de acordo com a literatura. A determinação qualitativa da oxamniquina nas amostras foi realizada por identificação de grupos funcionais da molécula e usando técnicas instrumentais. O doseamento da matéria-prima foi realizado por espectrofotometria...

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Cromatografia liquida de alta eficiencia e utilizada para identificacao do terconazol na materia prima e determibacao quantitativa deste farmaco nas especialidades farmaceuticas de creme e ovulo. A analise do terconazol por CLAE apresenta resultados que comprovam a exatidao e precisao do metodo proposto. os resultados de recuperacao analisados, com valor medio de 99,33 por cento e 99,89 por cento para as especialidades farmaceuticas ovulos e creme, respectivamente, nos permitem indicar a cromatografia liquida de alta eficiencia como metodo ideal para determinacao do terconazol nas formas farmaceuticas comercializadas no Brasil

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As doenças causadas por fungos têm ocorrido com maior freqüência, nos últimos anos, devido a mudanças de hábitos das pessoas, principalmente a liberaçäo sexual. Na tentativa de resolver este desafio terapêutico, os pesquisadores passaram a desenvolver novos antifúngicos. Dentre estes, surgiu o terconazol, primeiro membro da nova classe de compostos triazólicos. É muito eficaz em sua açäo tópica, possui amplo espectro, constituindo-se em fármaco de primeira escolha no tratamento de várias micoses

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