Estudo de degradação forçada e de compatibilidade do ciprofibrato com excipientes farmacêuticos

Abstract

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.