RESUMO
The intramuscular administration of the injectable suspension betamethasone sodium phosphate (BSP) and betamethasone dipropionate (BD) has immediate therapeutic activity due to solubilized BSP and prolonged activity resulting from the slow release of BD micro-crystals. The purpose of this study was to develop and validate a dissolution method for BD in intramuscular injectable suspensions with detection by high-performance liquid chromatography (HPLC) method. Five commercial products presented a distribution of particle sizes, ranging between 7.43 and 40.25 µm as measured by laser diffraction. It was also found that particle sizes differed between batches of the same product. The different products were tested using the paddle apparatus, with stirring speeds of 25 and 50 rpm in 300 mL of phosphate buffer; simulated body fluid, muscle fluid, and synovial fluid were used as biorelevant dissolution media at 37±0.5°C. It was verified that not only does average particle size affect the dissolution rate, but also the mode and the polydispersity index of the particles. Discriminatory power was obtained using the in vitro dissolution method with 0.1 M sodium phosphate buffer pH 7.4 containing 0.1% sodium lauryl sulfate and a stirring speed of 50 rpm. The HPLC-method is linear, precise, selective, and accurate for the quantification of BSP and BD in dissolution profile testing. This dissolution method can be utilized as a method to control the quality of these injectable suspensions.
Assuntos
Betametasona/análogos & derivados , Betametasona/administração & dosagem , Betametasona/química , Cromatografia Líquida de Alta Pressão , Injeções Intramusculares , Tamanho da Partícula , SolubilidadeRESUMO
Betamethasone is a synthetic corticosteroid designed to exert a marked glucocorticoid activity. As the free alcohol, betamethasone finds widespread clinical applications related to its anti-inflammatory and immunosuppressant activity. In the present study, a fast, sensitive, robust method was developed for the determination and quantification of betamethasone in human plasma by liquid chromatography coupled with tandem mass spectrometry, using photospray ionization in negative mode. Betamethasone was extracted from 0.5 ml human plasma by liquid-liquid extraction (LLE) using chloramphenicol as internal standard. The method has a chromatographic run of 2.5 min using a C(18) analytical column (100 mm x 2.1 mm i.d.) and the linear calibration curve over the range was linear from 0.05 to 50 ng ml(-1) (r(2)>0.993). The between-run precision, based on the relative standard deviation replicate quality controls was 94.1% (0.15 ng ml(-1)), 90.7% (4.0 ng ml(-1)) and 97.2% (40 ng ml(-1)). The between-run accuracy for the above-mentioned concentrations was 11.9, 9.0 and 9.8%, respectively. The method herein described was employed in a bioequivalence study of two formulations of dexchlorpheniramine/betamethasone 2 mg/0.25 mg tablets.
Assuntos
Betametasona/sangue , Cromatografia Líquida de Alta Pressão/métodos , Espectrometria de Massas por Ionização por Electrospray/métodos , Betametasona/química , Humanos , Sensibilidade e Especificidade , Equivalência TerapêuticaRESUMO
Five electrokinetic chromatography systems were compared concerning retention behavior and lipophilicity. Comparison was based on capacity (retention) factors of some steroidal drugs, and on log P(OW) values derived by the aid of reference substances. In all systems the aqueous buffer consisted of phosphate (20 mM, pH 7.5). Two systems had micelles, three systems microdroplets as negatively charged pseudostationary phases. The micelles were formed by sodium dodecyl sulfate (SDS) and sodium cholate, respectively. One microemulsion consisted (as usual) from octane as oil, butanol as cosurfactant and SDS as charged tenside. Two microemulsions were made from biosurfactants (phosphatidylcholine, isopropylmyristate) to better simulate biopartitioning of the drugs. Even for noncharged analytes a change in migration sequence and thus in log P(OW) was observed for the systems consisting of the biosurfactants, compared to the others. For the former systems, log P(OW) derived from the capacity factors agree for all analytes with those obtained from calculation by computer software based on the structure of the drugs, and with experimental data directly obtained from octanol/water partitioning.
Assuntos
Betametasona/análogos & derivados , Betametasona/química , Cromatografia Capilar Eletrocinética Micelar/métodos , Emulsões/química , Sensibilidade e EspecificidadeRESUMO
The aim of this work was to develop an analytical method for a simultaneous determination of cyanocobalamin (Vitamin B12), betamethasone, and diclofenac, present in pharmaceutical formulations, by high performance liquid chromatography, assuring rapidity, accuracy, precision, and selectivity. The working conditions were as follows: RP18 column of 125 mm x 4 mm ID and a particle size of 5 microm; mobile phase acetonitrile-water (40:60; v/v) (pH* 3.45) adjusted with acetic acidl flow gradient from 0.8 to 1.9 ml/min.; injection volume of 20 microl; temperature 34 degrees C and detection at 240 nm. The method was adequately validated, and linearity, accuracy, as well as the system, method and interday precision, for each active principle, were determined.