RESUMO
Diabetes mellitus is a chronic disease with high and growing prevalence worldwide. Therefore, the development of fast and efficient methods for the QC of antidiabetic drugs is of fundamental importance. Two ultra-fast methods, using a conventional (C18 100 × 2.1 mm, 5 µm fully porous particle) column or a fused-core (C18 100 × 2.1 mm, 2.7 µm fused-core particle) column, were developed for the simultaneous determination of four antidiabetic drugs (chlorpropamide, glibenclamide, gliclazide, and glimepiride). The developed methods were compared in terms of efficiency, speed of analysis, resolution, and peak symmetry. Both methods were validated with respect to selectivity, system suitability, linearity, precision, accuracy, LOD, LOQ, and robustness, using glibenclamide as model. Conventional and fused-core methods were shown to be appropriate for the determination of glibenclamide in tablets; however, the fused-core column presented higher efficiency, detectability, and resolution. Also, it enabled faster analysis, with separation of the four drugs in less than 1 min.
Assuntos
Glibureto/análise , Hipoglicemiantes/isolamento & purificação , Porosidade , Dióxido de SilícioRESUMO
Alguns insumos farmacêuticos ativos (IFA) possuem como característica, a possibilidade de apresentarem o polimorfismo, que pode se desenvolver em alguma das etapas do processo de produção na indústria. No caso deste não ser caracterizado e especificado, um diferente polimorfo poderá ser utilizado equivocadamente durante o processo de fabricação. A ocorrência de polimorfismo pode originar importantes variações nas propriedades físico-químicas dos IFAs, principalmente quanto à solubilidade. Alguns medicamentos de glibenclamida (GLIB) apresentaram denúncias de ineficácia terapêutica e a presença de polimorfos pode ser uma das possíveis causas. Neste trabalho foram analisados cinco medicamentos e cinco IFAS de diferentes fornecedores. Para os medicamentos foram feitos testes característicos de verificação de equivalência farmacêutica. Nos IFAS, as diversas técnicas empregadas não evidenciaram presença de polimorfos ou alterações importantes nas propriedades físico-químicas e na velocidade de dissolução intrínseca. Entretanto, os perfis de dissolução dos medicamentos, principalmente, entre os dois similares A e B demonstraram diferenças apontadas pelos valores do fator f2, respectivamente, de 20 e 42, os quais indicaram associação destes valores com a presença de distintos excipientes, como por exemplo o manitol e diferentes processos de produção industrial.
Some active pharmaceutical ingredients (API) might present polymorphism at any stage of the industryproduction process. In caseit is not characterized and specified, a different polymorph might beerroneously used during the manufacturing procedure. Polymorphisms cause some variations in thephysicochemical properties of APIs, especially in solubility. Therapeutic inefficacy was detected in someglyburide drug products, and the occurrence of polymorphs might be one of the possible reasons. Thisstudy analyzed five drug products and five APIs., The characteristic pharmaceutical equivalence testswere used for analyzing the drug products. The techniques employed to evaluate the APIs showed nodifferences in polymorphism, no significant changes in the physicochemical properties or in the intrinsicdissolution rate. However, the dissolution profiles of the drug products, mainly between two similarproducts A and B, showed significant differences in the f2 factor values, being 20 and 42, respectively,indicating that these values were related to the occurrence of different excipients, such as mannitol.
Assuntos
Dissolução , Glibureto/análise , Insumos Farmacêuticos , Medicamentos Genéricos , Medicamentos Similares , CristalizaçãoRESUMO
This study describes a method for non-destructive detection of adulterated glibenclamide tablets. This method uses near infrared spectroscopy (NIRS) and fluorescence spectroscopy along with chemometric tools such as Soft Independent Modeling of Class Analogy (SIMCA), Partial Least Squares-Discriminant Analysis (PLS-DA) and Unfolded Partial Least Squares with Discriminant Analysis (UPLS-DA). Both brand name (Daonil) and generic glibenclamide tablets were used for analysis. The levels of glibenclamide in each type of tablet were evaluated by derivative spectrophotometry in the ultraviolet region. The results obtained from the NIR and fluorescence spectroscopy along with those obtained from multivariate data classification show that this combined technique is an effective way to detect adulteration in drugs for the treatment of diabetes. In the future, this method may be extended to detect different types of counterfeit medications.