Determination of the melting temperature, heat of fusion, and purity analysis of different samples of zidovudine (AZT) using DSC

Abstract

The determination of chemical purity, melting range, and variation of enthalpy in the process of characterizing medicines is one of the principal requirements evaluated in quality control of the pharmaceutical industry. In this study, the method of purity determination using DSC was outlined, as well as the application of this technique for the evaluation of commercial samples of zidovudine (AZT) (raw material) supplied by different laboratories. To this end, samples from six different laboratories (A, B, C, D, E, and F) and the standard reference (R) from the United States Pharmacopeia (USP) were analyzed. The DSC curves were obtained in the temperature range of 25 to 200 o C under the dynamic atmosphere of N 2 (50 mL min , using an Al capsule containing approximately 2 mg of sample material. The results demonstrated that the standard reference presented a proportion of 99.83% whereas the AZT samples presented a variation ranging from 97.59 to 99.54%. In addition, the standard reference was found to present a temperature of onset of melting point of 122.80 °C. Regarding the samples of active agents provided by the different laboratories, a variation ranging from 118.70 to 122.87 °C was measured. In terms of DH m , the samples presented an average value of 31.12 kJ mol -1.Uniterms: Zidovudine/purity determination. Differential scanning calorimetry. Thermal analysis. Medicines/quality control. Medicines/qualitative analysis.A determinação da pureza química, a faixa de fusão e a variação de entalpia envolvida no processo de caracterização de fármacos é um dos principais requisitos avaliados no controle de qualidade em indústrias farmacêuticas. Neste trabalho é feita uma breve abordagem sobre o método de determinação de pureza utilizando DSC, assim como a aplicação desta técnica para avaliação de amostras comerciais de zidovudina (AZT) (matéria-prima) fornecida por diferentes laboratórios. Para tal, foram analisadas amostras de seis diferentes laboratórios (A,B,C,D,E e F) e a substância química de referência (R) da United States Pharmacopeia (USP). As curvas DSC foram obtidas na faixa de temperatura entre 25 a 200 o C, sob atmosfera dinâmica de N 2 (50 mL min -1 ), b=2 o C min -1 , utilizando cápsula de Al contendo aproximadamente 2 mg de amostra. De acordo com os resultados, pode-se observar que a substância química de referência apresentou teor igual a 99,83% e que as amostras de AZT apresentaram uma faixa de variação entre 97,59 e 99,54%. Pode-se verificar, ainda, que a substância química de referência apresentou uma temperatura onset de fusão igual a 122,80 °C. Para as amostras dos princípios ativos fornecidos pelos diferentes laboratórios, pode-se verificar uma faixa de variação entre 118,70 e 122,87 °C. No que se refere ao DH m , as amostras apresentaram valor médio de 31,12 kJ.mol -1 .Unitermos: Zidovudina/determinação da pureza. Calorimetria exploratória diferencial. Análise térmica. Medicamentos/controle de qualidade. Medicamentos/análise qualitativa.

Thermal characterization of some guanylhydrazones by thermal and nonthermal techniques

“…Araújo et al have used DSC for determining the purity of substances with a fast and reliable technique for eutectic systems, in which melting is not accompanied by thermal decomposition of the material. Those authors found that the main advantages of the DSC, over chromatography and spectroscopy, are that the analysis of all the impurities normally does not require standards except, for the main compound, and permits simultaneous measurements of the melting range and variation of enthalpy [35]. The sample WE010 showed a purity of 98.87 %.…”

“…Many authors have used the thermal and nonthermal techniques in the physicochemical characterization of herbal products [35], as well as of other synthetic substances with biological activity potential [28][29][30][31][32]. All those studies showed the relevance of the thermal analysis in the determinations of the thermal parameters and stabilities of those products.…”

“…Other analytic non-thermal techniques have been used to identify and quantify samples with HPLC and FTIR [35,36]. However, there are no studies with these guanylhydrazones by techniques cited above.…”

Thermoanalytical Study and Purity Determination of Azelastine Hydrochloride and Emedastine Difumarate

“…There are definitive advantages to employing multiple thermal analysis methods to attain varying views of the physicochemical properties of pharmaceuticals. The determination of the key physical and chemical properties of a new material is essential [16][17][18][19][20][21][22][23].…”

“…The melting transitions of a pure 100% crystalline material should be infinitely sharp, but impurities or defects in the crystal structure will broaden the melting range and lower the final melting point to a temperature lower than T o [23]. Purity determination is officially listed in Merk index [25].…”