Guanylhydrazones are molecules with great pharmacological potential in various therapeutic areas, including antitumoral activity. Factorial design is an excellent tool in the optimization of a chromatographic method, because it is possible quickly change factors such as temperature, mobile phase composition, mobile phase pH, column length, among others to establish the optimal conditions of analysis. The aim of the present work was to develop and validate a HPLC and UHPLC methods for the simultaneous determination of guanylhydrazones with anticancer activity employing experimental design. Precise, exact, linear and robust HPLC and UHPLC methods were developed and validated for the simultaneous quantification of the guanylhydrazones LQM10, LQM14, and LQM17. The UHPLC method was more economic, with a four times less solvent consumption, and 20 times less injection volume, what allowed better column performance. Comparing the empirical approach employed in the HPLC method development to the DoE approach employed in the UHPLC method development, we can conclude that the factorial design made the method development faster, more practical and rational. This resulted in methods that can be employed in the analysis, evaluation and quality control of these new synthetic guanylhydrazones.

Isoniazid and rifampicin are considered the first-line medication for preventing and treating tuberculosis. Rifampicin is degraded in the stomach acidic environment, especially when combined with isoniazid, factor contributing to treatment failure. In this study, gastric-resistant isoniazid pellets were obtained to physical contact of this drug with rifampicin and to bypass the stomach´s acidic environment. The pellets were fabricated using the extrusion-spheronization technique. The coating process was conducted in a fluid spray coater using Acrycoat L 100 ® solution as the coating agent. The pellets obtained were submitted to a dissolution test in HCl 0.1 N and phosphate buffer media. The results indicated that optimum gastric-resistance was only attained with the highest amount of coating material, with isoniazid almost fully released in phosphate buffer. The amount of rifampicin released from its mixture with non-coated isoniazid pellets in HCl 0.1 N was less than that released from its mixture with the entericcoated pellets. Acrycoat L 100 ® was shown to be an effective enteric/gastric-resistant coating since the stability of rifampicin appeared to be enhanced when physical contact of this drug with isoniazid was prevented at low pH. Uniterms:Rifampicin. Gastric-resistant isoniazids/pellets. Pellets/enteric coating. Acrycoat L 100®/ use/enteric coating.Isoniazida e rifampicina são fármacos de primeira escolha para a prevenção e tratamento da tuberculose. A rifampicina degrada-se em condições ácidas do estômago, principalmente na presença da isoniazida, o que contribui para a falha do tratamento. O presente trabalho teve como objetivo a obtenção de péletes de isoniazida gastrorresistentes, visando a evitar contato da rifampicina com isoniazida e consequente degradação no meio ácido estomacal. Os péletes foram produzidos pela técnica de extrusão-esferonização. O processo de revestimento foi conduzido em leito fluidizado com solução orgânica de Acrycoat L 100 ® . Os péletes obtidos foram submetidos ao teste de dissolução em HCl 0,1 N e tampão fosfato. Os resultados indicam que a gastrorresistência foi obtida somente com a maior quantidade de revestimento, sendo a isoniazida liberada completamente no meio tampão fosfato. A quantidade de rifampicina dissolvida em meio ácido, quando associada a péletes de isoniazida não revestidos, foi menor do que a observada na presença de péletes de liberação entérica. O polímero Acrycoat L 100® mostrou-se eficiente para o recobrimento com a função de gastrorresistência, indicando que a instabilidade da rifampicina pode ser reduzida nas associações com a isoniazida através do revestimento entérico da isoniazida.Unitermos: Rifampicina. Isoniazidas gastrorresistentes/péletes. Péletes/revestimento entérico. Acrycoat L 100®/uso/revestimento entérico.

2-[(3,5-di-tert-butyl-4-hydroxyphenyl)methylene]-hydrazinecarboximidamide (WE010), 2-([1,1 0 -biphenyl]-4-ylmethylene)-hydrazinecarboximidamide (WE014), and 2-[(3,4-dichlorophenyl)methylene]-hydrazinecarboximidamide (WE017) are guanylhydrazone derivatives widely studied biologically and chemically; however, there are no studies regarding their thermal behaviors. The present study aims to apply the thermal analyses: differential scanning calorimetry (DSC), differential scanning calorimetry coupled to the photovisual system (DSC-photovisual), and thermogravimetry (TG), to characterize the guanylhydrazones, as well as HPLC and FTIR. The DSC curve of WE010 shows a melting process with T onset at 190°C and peak at 193.5°C (DH 41.0 J g -1 ). Due to the symmetry of the melting peaks obtained by DSC, it is possible to calculate the purity of the sample (98.87 %). The DSC curve of WE014 shows the melting process in the range of 208-213°C, with a melting peak at 211°C (DH 61 J g -1 ).The DSC curve of WE017 showed T onset at 215°C and peak temperature of 219°C (DH 55 J g -1 ). The TG curve of WE010, WE014, and WE017 presents initial decomposition temperatures of 186.95, 197.31, and 195.44°C, respectively. The DSC-photovisual confirmed the results of DSC and TG. The HPLC determined the purities of the samples and confirmed the results of DSC. The FTIR confirmed the thermal data. Thus, the use of thermal analysis is an important tool for the characterization of molecules with therapeutic potential contributing to the characterization and evaluation of their stability as well as nonthermal technique with complementary tool.