Evaluation and correlation of the physicochemical properties of carvedilol.
Carvedilol is an antihypertensive drug with non-selective blockade (moderate selectivity for β1 and β2 adrenoceptors) and vasodilating properties due to α receptor blockade. Its molecule has one chiral centre; therefore, the drug has two enantiomers. Furthermore, it presents different polymorphs depending on the synthesis route and crystallization procedure. Carvedilol is a weak base that is substantially insoluble in water, acidic solutions, and gastric and intestinal fluids; it is classified as a Class II drug in the Biopharmaceutical Classification System. The solubility of carvedilol varies according to the solvent pH. This study aimed to evaluate and correlate the physicochemical and processability properties of carvedilol. Samples of the active ingredient from three different manufacturers were characterized according to their flowability, particle size and apparent density and using microscopy, differential scanning calorimetry (DSC), thermogravimetric analysis, X-ray diffraction, Fourier transform infrared spectroscopy, intrinsic dissolution and powder dissolution tests. It was determined that the tested samples presented the same polymorphic form, did not present good flowability, and presented different particle size distributions. The tests to evaluate flowability and compressibility were shown to be discriminative, and slight differences among the samples were noted.
a Departamento de Desenvolvimento Farmacotécnico , Medquímica Indústria Farmacêutica S/A , Minas Gerais , Brazil.|b Mestrado Profissional em Gestão, Pesquisa e Desenvolvimento na Indústria Farmacêutica - Farmanguinhos, Fundação Oswaldo Cruz , Rio de Janeiro , Brazil.
Josyane Márcia Vasconcelos
JM
Alves
c Laboratório de Sistemas Farmacêuticos Avançados, Farmanguinhos - Fundação Oswaldo Cruz , Rio de Janeiro , Brazil , and.
Livia Deris
LD
Prado
b Mestrado Profissional em Gestão, Pesquisa e Desenvolvimento na Indústria Farmacêutica - Farmanguinhos, Fundação Oswaldo Cruz , Rio de Janeiro , Brazil.|d Laboratório de Sistemas Farmacêuticos Avançados, Farmanguinhos - Fiocruz , Rio de Janeiro , Brazil.
Helvécio Vinícius Antunes
HV
Rocha
D002152:Calorimetry, Differential Scanning / Q000379:methods; D002227:Carbazoles / Q000737:chemistry*; D000077261:Carvedilol; D002626:Chemistry, Pharmaceutical / Q000379:methods; D003460:Crystallization; D008855:Microscopy, Electron, Scanning / Q000379:methods; D010316:Particle Size; D033362:Powder Diffraction / Q000379:methods; D011208:Powders / Q000737:chemistry; D011412:Propanolamines / Q000737:chemistry*; D012995:Solubility; D012997:Solvents / Q000737:chemistry; D017550:Spectroscopy, Fourier Transform Infrared / Q000379:methods; D013678:Technology, Pharmaceutical / Q000379:methods; D014961:X-Ray Diffraction / Q000379:methods
D002227:Carbazoles; D011208:Powders; D011412:Propanolamines; D012997:Solvents; D000077261:Carvedilol
Carvedilol; characterization; dissolution; flowability; polymorphism; raw material