Estudo de degradação forçada e de compatibilidade do ciprofibrato com excipientes farmacêuticos
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2022-08-31
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Universidade Federal de Goiás
Resumo
Ciprofibrate-CPF is a hypolipidemic that promotes the reduction of serum
levels of cholesterol and triglycerides by stimulating activated nuclear
receptors for peroxisome proliferation-alpha-PPAR-α. In this work, the stability
of CPF was studied using forced degradation and compatibility studies. The
Active Pharmaceutical Ingredient-API (SQC) was characterized by
Thermogravimetric Analysis/Derivative Thermogravimetric AnalysisTGA/DTGA, Differrential Scanning Calorimetry-DSC, Differrential Scanning
Calorimetry coupled to the Photovisual system-DSC-Photovisual, Absorption
spectroscopy in the mid-infrared region with Fourier Transform-FTIR, Nuclear
Magnetic Resonance-RMN, Powder X-ray Diffractometry-DRXP, High
Resolution Mass Spectrometry-EMAR and High Performance Liquid
Chromatography coupled with Diode Array Detector and High Resolution Mass
Spectrometry-CLAE/DAD/EMAR. The forced degradation study was carried
out for CPF (SQC) under the following conditions: acid hydrolysis, basic
hydrolysis, oxidative and thermal at 70 °C 240 hours using EMAR and
CLAE/DAD/EMAR. The compatibility study between the CPF and the
excipients was carried out by preparing binary mixtures in the proportions
50:50 and 92:08 (m/m), where the isolated components (CPF (SQT) and
excipients), Simulated Excipients Sample-ASE (excipients) and the binary
mixtures (CPF-excipient or CPF-excipients) were analyzed by TGA/DTGA,
DSC, DSC-Photovisual, FTIR, and DRXP. The EMAR and CLAE/DAD/EMAR
results suggested the degradation of CPF when subjected to basic hydrolysis,
with some degradation products previously reported in the literature being
observed and a new product identified. In the other exposure conditions, the
CPF remained stable. The DSC technique suggested signs of interaction
between the CPF and the excipients (Sodium Starch Glycolate-AGS, Sodium
Lauryl Sulfate-LSS, Silicon Dioxide-DOS and Hydrogenated Vegetable OilOVH) when prepared in a proportion 50:50 (m/m) and between CPF and the
excipient (OVH) in a proportion (92:08 m /m). However, the FTIR and DRXP
techniques did not confirm the sings of interaction observed in the DSC, except
when DOS was used at 50%. The compatibility study indicated the use of the
CPF-ASE binary mixture in the proportion 50:50 (m/m) as a candidate for
pre-formulation.
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BRITO, C. C. S. M. Estudo de degradação forçada e de compatibilidade do ciprofibrato com excipientes farmacêuticos. 2023. 247 f. Tese (Doutorado em em Química) - Instituto de Química, Universidade Federal de Goiás, Goiânia, 2022.