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.

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.

This work describes the establishment of dissolution test conditions for 75 mg cinnarizine capsules using a multivariate approach. A 2³ full factorial design was carried out to achieve the best conditions and HCl 0.1 mol L-1 as dissolution medium, basket as apparatus at 100 rpm and collect time at 30 min were considered adequate. The quantification was carried out by spectrophotometry at 251 nm. Both dissolution procedure and analytical method were validated and all parameters were within the acceptable limits. Since there is no official monograph for this pharmaceutical product, this dissolution test could be applied for quality control routine.

This work describes the development and validation of a dissolution test for 60 mg of diltiazem hydrochloride in immediate release capsules. The best dissolution in vitro profile was achieved using potassium phosphate buffer at pH 6.8 as the dissolution medium and paddle as the apparatus at 50 rpm. The drug concentrations in the dissolution media were determined by UV spectrophotometry and HPLC and a statistical analysis revealed that there were significant differences between HPLC and spectrophotometry. This study illustrates the importance of an official method for the dissolution test, since there is no official monograph for diltiazem hydrochloride in capsules.

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 necessitam de reagentes poluentes e requerem equipamentos economicamente viáveis.

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.

This work describes the development and validation of a dissolution test for 50 mg losartan potassium capsules using HPLC and UV spectrophotometry. A 2(4) full factorial design was carried out to optimize dissolution conditions and potassium phosphate buffer, pH 6.8 as dissolution medium, basket as apparatus at the stirring speed of 50 rpm and time of 30 min were considered adequate. Both dissolution procedure and analytical methods were validated and a statistical analysis showed that there are no significant differences between HPLC and spectrophotometry. Since there is no official monograph, this dissolution test could be applied for quality control routine.

This work describes the validation of a method for quantification of famotidine in capsules by UV spectrophotometry using as solvents buffer solution at pH 2.5 and buffer solution at pH 4.5. The results show that the method is practical, selective, accurate, precise and linear from 10.0 to 25.0 µg/mL of famotidine in both solvents. However, a variance analysis showed a lower mean percentage of famotidine when buffer at pH 2.5 is used. This effect was attributed to the instability of famotidine in acidic media. Therefore, the use of pH 4.5 buffer was considered suitable for analysis of famotidine in capsules.

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% 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.

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% 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.

Itraconazole is a synthetic antifungal drug administered orally with a broad spectrum of activity against mycotic infections. The present work consists of the development and validation of analytical methodology for evaluation of itraconazole in pharmaceutical products by high performance liquid chromatography. The separation was made using the reversed-phase column LC-18, acetonitrile/diethylamine 0.05% v/v, 60:40 v/v, pH 8.0 as mobile phase, methanol as solvent and detection and quantification at 254 nm. The results here obtained show that the analytical methodology is accurate, reproducible, robust and linear over the concentration range 8.0-12.0 µg/mL of itraconazole. The method was applied to pharmaceutical capsules containg itraconazole pellets and showed to be efficient, yielding good results.

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. Entre as provas de identificação pode-se reconhecer o fármaco por reações químicas de grupos funcionais e por técnicas instrumentais. Para determinação quantitativa do fluconazol na matéria-prima, empregou-se a volumetria com ácido perclórico, em meio acético e detecção do ponto final por indicadores e a espectrofotometria na região do ultravioleta, utilizando hidróxido de sódio 0,1 M a 261 nm. Os parâmetros estabelecidos para o controle de qualidade das amostras de cápsulas dos laboratórios analisados foram aspecto, variação do peso, desintegração, teste de dissolução e perfil de dissolução. O método de doseamento do fluconazol, na forma farmacêutica cápsula, por espectrofotometria na região do ultravioleta apresentou linearidade, especificidade, precisão e exatidão dentro dos critérios de aceitação. Os lotes dos laboratórios C, D apresentaram perfis de dissolução similares ao medicamento de referência (laboratório E), demonstrando haver um comportamento homogêneo para estes medicamentos. Os lotes dos laboratórios A e B não apresentaram homogeneidade quanto ao perfil de dissolução, quando comparado com os demais laboratórios.

Fluconazole is a triazole derivated drug with an antifungal activity which is used in the treatment of a large variety of fungal infections. The objective of this work is to establish parameters for the quality control of fluconazole itself, and the pharmaceutical specialities capsules, for elaboration of a monography for Brazilian Pharmacopeia. The raw material of fluconazol was characterized by the following tests: aspect, solubility and fusion range. The fluconazol impurities can be detected through limit assay of chloride, sulphate, iron, heavy metals, lost on drying and residue on ignition. Among the identification tests this drug can be recognized by chemical reactions of functional groups and instrumental methods. To determine the quantitative value of fluconazol in raw material it was used perchloric acid volumetry in acetic medium and period detection by indicators and ultraviolet spectrophotometry utilizing 0,1 M sodium hydroxide in 261 nm was used. Capsules samples from the analysed were aspect, average weight determination, disintegration, dissolution test and dissolution profile. The determination of drug in capsules by ultraviolet spectrophotometry demonstrated linearity, specificity, precision and accuracy. The lots of C, D, and E laboratories showed similar release profiles demonstrating a homogeneous behaviour. The lots of A and B laboratories did not show homogeneity in dissolution profile when compared to other laboratories.