Dissolution test optimization for meloxicam in the tablet pharmaceutical form

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.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

Analysis of spironolactone polymorphs in active pharmaceutical ingredients and their effect on tablet dissolution profiles

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

Validação de método espectrofotométrico na região do UV para quantificação de famotidina em cápsulas

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

Estabelecimento de condições para ensaio de dissolução de cápsulas de cinarizina empregando planejamento fatorial

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

Evaluating the discriminatory power of a dissolution assay for rosuvastatin calcium capsules: Solid-state properties and dissolution media

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 immediaterelease 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

Recent applications of analytical techniques for quantitative pharmaceutical analysis: A review

The intension of this paper was to review and discuss some of the current quantitative analytical procedures which are used for quality control of pharmaceutical products. The selected papers were organized according to the analytical technique employed. Several techniques like ultraviolet/visible spectrophotometry, fluorimetry, titrimetry, electroanalytical techniques, chromatographic methods (thin-layer chromatography, gas chromatography and high-performance liquid chromatography), capillary electrophoresis and vibrational spectroscopies are the main techniques that have been used for the quantitative analysis of pharmaceutical compounds. In conclusion, although simple techniques such as UV/VIS spectrophotometry and TLC are still extensively employed, HPLC is the most popular instrumental technique used for the analysis of pharmaceuticals. Besides, a review of recent works in the area of pharmaceutical analysis showed a trend in the application of techniques increasingly rapid such as ultra performance liquid chromatography and the use of sensitive and specific detectors as mass spectrometers

Development and validation of a dissolution test for diltiazem hydrochloride in immediate release capsules

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.Fundação de Amparo à Pesquisa do Estado de São Paulo (FAPESP)Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES

Chemical pharmaceutical analysis of fluconazole and its pharmaceutical speciality capsule

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 matériaprima 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

A first-derivative spectrophotometric method for the determination of ciprofloxacin hydrochloride in ophthalmic solution

A sensitive, economical and reproducible derivative visible-spectrophotometric method for determination of ciprofloxacin hydrochloride in ophthalmic solution was developed and validated. The method is based on the development of yellow colored product due the reaction between ciprofloxacin hydrochloride and Fe (III). After the reaction, the spectra of the solutions were recorded in the range of 360-500 nm and the first-derivative spectra were obtained by instrumental electronic differentiation using a delta lambda (Δλ) of 8 nm. Analytical responses were units of distance from the central zero base line to the negative peak obtained at 386.4 nm. The method was completely validated according to the ICH guidelines, showing accuracy, precision, selectivity, robustness and linearity. The proposed method is simple, of low cost and provides reliable results in order to be used in quality control of ophthalmic solutions containing ciprofloxacin hydrochloride as active substance.Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES