Banca de DEFESA: ISIS GOMES DOS SANTOS

Uma banca de DEFESA de MESTRADO foi cadastrada pelo programa.
DISCENTE : ISIS GOMES DOS SANTOS
DATA : 30/04/2019
HORA: 09:00
LOCAL: Faculdade de Farmácia
TÍTULO:

CHEMICAL-PHARMACEUTICAL ANALYSIS AND STABILITY STUDIES OF HYDROHYUREA IN RAW MATERIAL AND CAPSULES

PALAVRAS-CHAVES:

Hydroxyurea, validation, degradation products, stability indicating analytical method, high performance liquid chromatography, spectrophotometry.

PÁGINAS: 100
GRANDE ÁREA: Ciências da Saúde
ÁREA: Farmácia
SUBÁREA: Análise e Controle de Medicamentos
RESUMO:

Hydroxyurea (HU) is the therapeutic class of antimetabolites and acts on the cell cycle by inhibiting the ribonucleotide reductase enzyme present in DNA biosynthesis and maintaining it in the S phase. This drug is used in the treatment of neoplastic diseases such as myeloid leukemia, psoriasis and has recently shown great clinical efficacy in the treatment of sickle cell disease, being the only drug capable of reducing vascular occlusion effects and improving the quality of patients’ life. Despite the clinical importance of HU, the Brazilian Pharmacopoeia 5th edition (2010) does not present a monograph intended for this drug, nor does it exist in the scientific literature and official compendiums stability indicating analytical methods (SIAM) for HU. The development and validation of analytical methods for this molecule is justified by its therapeutic potential and the need for methods that prove its quality, with agility, low cost and lower environmental impact. In this work the qualitative analysis of the raw material and finished product was carried out, verifying the organoleptic characteristics, uniformity of weight for the capsules, identification by infrared (IR) and ultraviolet (UV) spectrophotometry and by high performance liquid chromatography  with photodiode array (HPLC - PAD). In addition, two analytical methods were developed and validated for the quantification of HU raw material and in capsules using UV spectrophotometry and HPLC-PDA, a technique used also in the forced degradation studies. The UV spectrophotometric method demonstrated that the most suitable solvent for the quantitative analysis of HU was water and the most appropriate wavelength was 213 nm. The method was selective, precise, accurate and robust. For the SIAM, chromatographic separation was obtained with Phenomenex® C18 column (250 x 4.6 mm, 5μm); the mobile phase was composed by water and ethanol (95:05, v/v), in isocratic mode. The flow rate was 0.5 mL/min and the wavelength was 214 nm. Forced degradation studies evidenced that HU degraded in oxidative medium, in basic and acid hydrolysis and was stable in thermal degradation. The SIAM for the quantification of HU was selective, linear, precise, accurate, sensitive and robust. The results of the methods development by UV spectrophotometry and HPLC-PAD for the quantitative analysis of HU were positive and met national and international quality requirements.

MEMBROS DA BANCA:
Presidente - 2053589 - EDITH CRISTINA LAIGNIER CAZEDEY
Interno - 2181841 - JOSE ANTONIO MENEZES FILHO
Externo à Instituição - ANIBAL DE FREITAS SANTOS JUNIOR - UNEB