Development of a dissolution test for lamotrigine in tablet form using an ultraviolet method

A finalidade deste estudo foi desenvolver e validar um método de dissolução para o fármaco lamotrigina na forma farmacêutica comprimido. Este método também foi utilizado para comparar o perfil de dissolução entre o Neural® e o produto de referência Lamictal®. O procedimento analítico foi realizado utilizando-se espectrofotometria de absorção no ultravioleta (267 nm) como forma de quantificação do fármaco. Após a determinação da solubilidade e das condições sink, os parâmetros selecionados foram: pás (50 rpm), 900 mL de ácido clorídrico 0.01 M e o tempo de 30 minutos (único ponto). Este método foi validado através da especificidade, linearidade, exatidão, precisão e robustez. A estabilidade da lamotrigina também foi avaliada no meio de dissolução.A dissolution test for tablets containing 100 mg of lamotrigine was developed and validated. The dissolution test was applied to compare the dissolution profile of Neural® with the reference product Lamictal®. The analysis procedure was carried out using a simple ultraviolet method at 267 nm. After the determination of solubility and sink conditions, the parameters selected were paddles at 50 rpm, 900 mL of 0.01 M hydrochloric acid, and 30 minutes duration (single point). This method was validated for specificity, linearity, accuracy, precision and robustness. Lamotrigine stability was also evaluated in dissolution medium

Gemifloxacin mesylate: UV spectrophotometric method for quantitative determination using experimental design for robustness

This study describes the validation of UV spectrophotometric method for quantitative determination of gemifloxacin mesylate (GFM) in tablets using methanol as solvent. The method was specific, linear, precise, exact and robust at 272 and 343 nm. The results confirmed that the method in both wavelengths is valid and useful to the routine quality control of GFM in coated tablets. The validate method was compared to liquid chromatography (HPLC), microbiological assay and visible (VIS) spectrophotometry, which were previously developed and validated to the same drug. There was not significative difference between the methods for GFM quantitation

Management of chemical residues : a necessity

A geração em grande escala e o armazenamento incorreto de resíduos químicos é um problema sério nas Instituições Superiores de Ensino. Devido a isto, este artigo apresenta sugestões para o gerenciamento e o descarte dos principais resíduos químicos gerados. Para iniciar um programa de gerenciamento é necessária a segregação dos diferentes tipos de resíduos químicos gerados, visando facilitar o seu tratamento e disposição final. Também são sugeridas algumas regras que deveriam ser seguidas para o correto armazenamento dos resíduos: desde a verificação da adequação do recipiente de armazenagem até a compatibilidade entre os resíduos armazenados. Em relação ao descarte, o artigo apresenta sugestões sobre o correto descarte ou o possível reaproveitamento de uma série de resíduos de diferentes classes químicas.The large scale generation of chemical residues and its storage constitute a serious problem in university laboratories. To initiate a residue management program, it's necessary to proceed a correct separation of the different kinds of chemical residues, in order to apply the best treatment and final disposition. In this paper, some attitudes are suggested towards the best way of discard toxic residues produced in chemistry laboratories. Some rules are also proposed, which may be follow in order to achieve a safe storage of chemical residues such as the simple verification of the possible compatibilities among the residues in storage. The authors suggest apropriate discard and adequate procedures for a series of residues of different chemical substances

UV SPECTROPHOTOMETRIC METHOD FOR QUANTITATIVE DETERMINATION OF BILASTINE USING EXPERIMENTAL DESIGN FOR ROBUSTNESS

Bilastine is a novel nonsedative H1-receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). This study describes the validation of an UV spectrophotometric method for quantitative determination of bilastine in tablets using 0.1 mol L-1 HCl as solvent. The method was specific, linear, precise, exact and robust at 210 nm, confirming that the method is fast and useful to the routine quality control of bilastine in tablets. The validate method was compared to liquid chromatography (HPLC), which was previously developed and validated to the same drug, and no significative difference between the methods using Student´s t test was found to bilastine quantitation.Bilastine is a novel nonsedative H1-receptor antagonist, which may be used for the symptomatic treatment of chronic idiopathic urticaria (CU). This study describes the validation of an UV spectrophotometric method for quantitative determination of bilastine in tablets using 0.1 mol L-1 HCl as solvent. The method was specific, linear, precise, exact and robust at 210 nm, confirming that the method is fast and useful to the routine quality control of bilastine in tablets. The validate method was compared to liquid chromatography (HPLC), which was previously developed and validated to the same drug, and no significative difference between the methods using Student´s t test was found to bilastine quantitation

Bilastine: stability-indicating a method using environmentally friendly by reversed-phase high-performance liquid chromatography (RP-HPLC)

This study describes the development and validation of a new environmentally friendly analytical method for the determination of bilastine in coated tablets and the evaluation of its capacity to be stability-indicating as well. The ecofriendly analytical method was validated by specificity, linearity, accuracy, precision and robustness by reversed-phase high-performance liquid chromatography (RP-HPLC) according to International Conference on Harmonization guidelines (ICH) and Association of Official Analytical Chemists (AOAC). Isocratic LC separation was achieved on a RP18 column using a mobile phase of sodium dihydrogen phosphate aqueous buffer solution adjusted to pH (6.0 ± 0.1) with o-phosphoric acid (85% v/v) and triethylamine (0,3% v/v) and ethanol (EtOH) in the following proportions (60:40 v/v), at a flow rate of 1.0 mL·min-1 at temperature-controlled at 30 °C. The analytical method showed selectivity, good recovery and precision (intra- and inter-day), robustness, and linear over a range from 5.0 to 50 μg·mL-1

Validation of UV spectrophotometric method for telithromycin in pharmaceutical formulations and comparison with HPLC and microbiological assay

An ultraviolet (UV) spectrophotometric method was developed for the analysis of telithromycin, member of the ketolides, in drug substance and coated tablets. The method validation yielded good results, such as the range, linearity, intra and inter-day precision, accuracy, recovery specificity, and robustness. UV spectrophotometric determinations were performed at 258 nm. Good linearity was obtained between 10.0 and 70.0/ μg mL. A prospective validation showed that the method is linear (r = 1) with precise relative standard deviation (RSD) of 0.4 %. The intra and inter-day precision values were < 2 % for all samples analyzed. The comparison between UV spectrophotometric, high performance liquid chromatography (HPLC) and microbiological assay showed no significant difference between the methodologies. The proposed method is appropriate for the determination of telithromycin in tablets and can be used in routine quality controlColegio de Farmacéuticos de la Provincia de Buenos Aire

Evaluation of the influence of fluoroquinolone chemical structure on stability: forced degradation and in silico studies

Fluoroquinolones are a known antibacterial class commonly used around the world. These compounds present relative stability and they may show some adverse effects according their distinct chemical structures. The chemical hydrolysis of five fluoroquinolones was studied using alkaline and photolytic degradation aiming to observe the differences in molecular reactivity. DFT/B3LYP-6.31G* was used to assist with understanding the chemical structure degradation. Gemifloxacin underwent degradation in alkaline medium. Gemifloxacin and danofloxacin showed more degradation perceptual indices in comparison with ciprofloxacin, enrofloxacin and norfloxacin in photolytic conditions. Some structural features were observed which may influence degradation, such as the presence of five member rings attached to the quinolone ring and the electrostatic positive charges, showed in maps of potential electrostatic charges. These measurements may be used in the design of effective and more stable fluoroquinolones as well as the investigation of degradation products from stress stability assays

Validation of an analytical method by high-performance liquid chromatography and microbiological assay, biological safety and in silico toxicity for danofloxacin

Danofloxacin is a veterinary fluoroquinolone used to treat respiratory and gastrointestinal diseases of birds, pigs and cattle. The literature reviewed shows some analytical methods to quantify this fluoroquinolone, but microbiological and biological safety studies are limited. The analytical methods were validated by the Official Codes. The LC-DAD method was developed and validated using an RP-18 column, mobile phase containing a mixture of 0.3% triethylamine (pH 3.0) and acetonitrile (85:15, v/v). The microbiological assay was performed by agar diffusion method (3 x 3) and Staphylococcus epidermidis as a microorganism test. Forced degradation studies were performed in both methods. The minimum inhibitory concentration (MIC) was performed by test microdilution and toxicity studies were evaluated using in silico study, cell proliferation, cell viability test, micronuclei and comet assay. LC and a microbiological assay proved linear, accurate, precise, and robust to quantify danofloxacin, but only the LC method showed selectivity to quantify the drug in the presence of its degradation products. These results demonstrate that the LC method is suitable for stability studies of danofloxacin, but a microbiological assay cannot be used to quantify the drug due to the biological activity of the photoproducts. Ex-vivo cytotoxicity and theoretical and experimental genotoxicity were also observed

Mesilato de gemifloxacino : desenvolvimento e validação de métodos analíticos, teste de dissolução e estudo de estabilidade

A análise de fármacos é fundamental nas diversas fases do desenvolvimento farmacêutico, tais como em estudos de formulação, estabilidade e controle de qualidade do produto. O mesilato de gemifloxacino (MGF), liberado para uso clínico no Brasil em novembro de 2006 com o nome comercial de Factive®, é uma fluorquinolona indicada para o tratamento da exacerbação aguda da bronquite crônica e da pneumonia adquirida da comunidade. A literatura pesquisada apresenta poucos relatos de determinação quantitativa e de estudos de estabilidade do fármaco em comprimidos revestidos. Anteriormente aos estudos, foi realizada a caracterização da substância química de referência (SQR) de MGF por espectrofotometria no infravermelho (E IV), ressonância magnética nuclear de hidrogênio (RMN 1H) e carbono (RMN 13C), análise térmica por calorimetria exploratória de varredura (DSC) e determinação da faixa de fusão. Métodos analíticos para determinação qualitativa e quantitativa foram desenvolvidos e validados por espectrofotometria na região do ultravioleta (E UV) e visível (E VIS), cromatografia líquida de alta eficiência (CLAE), eletroforese capilar (EC) e ensaio microbiológico pelo método de cilindros em placas. A validação de um método de dissolução baseado em dados in vivo do fármaco também foi realizada. A elucidação do produto de degradação isolado em condições alcalinas foi realizada por E IV, RMN de 1H, 13C e correlação (COSY, HSQC e HMBC), espectrometria de massas (EM) e emissão atômica. Estudos de citotoxicidade, fototoxicidade, genotoxicidade e fotogenotoxicidade foram empregados para conhecimento da toxicidade dos produtos analisados.The drug analysis is essential in all areas of the pharmaceutical development, such as during formulation studies, stability and quality control of the product. Gemifloxacin mesylate (GFM), approved for clinical use in Brazil in November of 2007 with the commercial name of Factive®, is a fluoroquinolone prescribed for the treatment of acute exacerbations of chronic bronchitis and community-acquired pneumonia. The research literature shows a few studies of quantitative determination and stabilities studies of the drug in coated tablets. Previously, it was performed the characterization of the reference chemical substance of GFM by infrared spectrometry (IR), nuclear magnetic resonance of 1H (1H NMR) and 13C (13C NMR), thermal analysis by differential scanning calorimetry (DSC) and determination of the melting range. Analytical methods for qualitative and quantitative determination were developed and validated by ultraviolet (UV) and visible (Vis) spectrophotometry, highperformance liquid chromatography (HPLC), capillary electrophoresis (CE) and microbiological assay applying the cylinder–plate method. The validation of the dissolution method based on in vivo data of the GFM was also performed. The elucidation of the isolate degradation product in alkaline conditions was performed by IR, 1H, 13C and correlation (COSY, HSQC and HMBC) NMR, and mass spectrometry (MS). Cytotoxicity, phototoxicity, genotoxicity and photogenotoxicity studies were carried out for the toxicity knowledge of the analyzed products