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Master's Dissertation
DOI
https://doi.org/10.11606/D.75.2024.tde-16072024-152141
Document
Author
Full name
Jonatha de Freitas
E-mail
Institute/School/College
Knowledge Area
Date of Defense
Published
São Carlos, 2024
Supervisor
Committee
Cavalheiro, Eder Tadeu Gomes (President)
Colman, Tiago André Denck
Gaglieri, Caroline
Title in Portuguese
Estudos termoanalíticos dos antivirais darunavir, ritonavir e sulfato de indinavir
Keywords in Portuguese
darunavir
espectrometria de massa
microscopia hot Stage
ritonavir
sulfato de indinavir
TGA-FTIR
Abstract in Portuguese
Os vírus tornaram-se um desafio para a sociedade contemporânea, tanto na saúde, quanto na economia e ciência. A presente dissertação envolve estudos termoanalíticos dos antivirais darunavir, ritonavir e sulfato de indinavir. Foi investigado o comportamento térmico desses fármacos por termogravimetria (TGA), termogravimetria derivada (DTG), análise térmica diferencial (DTA), calorimetria exploratória diferencial (DSC), termomicroscopia, espectrometria de massa (MS), difratometria de raios X em pó (PDRX) e termogravimetria acoplada ao espectrofotômetro na região vibracional do infravermelho (TGA-FTIR). O sulfato de indinavir apresentou perda de água fracamente ligada seguida de fusão em 149,6 °C e, imediatamente, decomposição em duas etapas. O ritonavir, após a fusão em 122,5 °C, se decompôs em duas perdas de massa. Já o darunavir apresentou perda de água fracamente ligada, seguida de fusão em 74,7 °C e decomposição com três etapas de perda de massa. Não houve evidências de recristalização durante o ciclo de resfriamento em nenhum dos fármacos. A partir das técnicas termoanalíticas e caracterização dos gases emanados, sugere-se que a decomposição do sulfato de indinavir se inicia com a liberação de água, dióxido de carbono, ácido isociânico, amônia, 2-indanol e 2-pentanol. Em temperaturas mais elevadas, há a continuação da saída de água, ácido isociânico, dióxido de carbono, amônia e 2-pentanol, todavia, percebeu-se, também, a presença de sulfeto de carbonila. O ritonavir se decompõe liberando como produtos gasosos a água, 5-metil tiazol, dióxido de carbono, sulfeto de carbonila, etanamina, formamida, benzeno e 2-isopropil-4-metil tiazol. Esquemas para a decomposição térmica do sulfato de indinavir e ritonavir foram propostos.
Title in English
Thermoanalytical studies of antivarirals darunavir, ritonavir and indinavir sulfate
Keywords in English
darunavir
hot stage microscopy
mass spectrometry
ritonavir
sulfato de indinavir
TGA-FTIR
Abstract in English
Viruses have become a challenge to contemporary society, both in health and in the economy and science. The present dissertation involves thermoanalytical studies of the antivirals darunavir, ritonavir, and indinavir sulfate. Thermal behavior and other properties of these drugs were investigated by thermogravimetry (TGA), derivative thermogravimetry (DTG), differential thermal analysis (DTA), differential scanning calorimetry (DSC), hot stage microscopy (HSM), mass spectrometry (MS), X-ray diffractometry (XRD), and thermogravimetry coupled to the spectrophotometer in the infrared vibrational region (TGA-FTIR). Indinavir sulfate presented weakly water loss followed by melting at 149.6 °C and immediately decomposed in two steps. Ritonavir, after melting at 122.5 °C, decomposed in two mass loss steps. Darunavir dehydrated losing a weakly water loss, followed by melting at 74.7 °C and decomposition with three mass loss steps. There was no evidence of recrystallization during in the cooling cycle for these drugs. Based on thermoanalytical techniques and characterization of evolved gases, it is suggested that the decomposition of indinavir sulfate start with the release of water, carbon dioxide, isocyanic acid, ammonia, 2-indanol, and 2-pentanol. At higher temperatures, there is a continued releasing of water, isocyanic acid, carbon dioxide, ammonia, and 2-pentanol; however, the presence of carbonyl sulfide was also observed. Ritonavir decomposes, releasing water, 5-methylthiazole, carbon dioxide, carbonyl sulfide, ethanamine, formamide, benzene, and 2-isopropyl-4-methylthiazole as gaseous products. Schemes for the thermal decomposition of indinavir sulfate and ritonavir were proposed.
 
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Publishing Date
2024-07-19
 
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