Estudo comparativo de duas formas farmacêuticas de cloridrato de diltiazem: aplicação de método analítico desenvolvido e validado visando o controle de qualidade

• Ano de defesa: 2014
• Autor(a) principal: Mateus Araújo Castro e Souza
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Minas Gerais; UFMG
• Palavras-chave em Português: Método analítico; CLAE; Controle de qualidade; Comprimidos; Perfil de dissolução; Cloridrato de diltiazem; Dissolução; Cápsulas magistrais; Farmácia
• Link de acesso: http://hdl.handle.net/1843/EMCO-9QRP6H

Diltiazem is a calcium channel antagonist used in the treatment of cardiac arrhythmias, hypertension and prevention of angina. Several analytical methods were found for the determination of diltiazem in tablets and for the determination of related substances in active pharmaceutical ingredient, but only one stability indicator analytical method has been found, being time-consuming and incompatible for liquid chromatography tandem mass spectrometry. The diltiazem hydrochloride compounded capsules are manipulated in the same dosages than immediate release tablets available in the market (30 and 60 mg) and are used interchangeably with the reference drug. Nevertheless, a comparison of the dissolution profiles of tablets and capsules is not described in the literature. In this work, a stability indicator analytical method for diltiazem hydrochloride determination in tablets and capsules by high performance liquid chromatography (HPLC) was developed and validated. The analytical method parameters of selectivity in relation to the formulation excipients and degradation products, linearity, precision, accuracy and robustness were evaluated according to the regulations. The analytical method was suitable for use in drug stability studies. In addition, samples of diltiazem hydrochloride generic and reference tablets and compounded capsules were evaluated by uniformity of weight, disintegration, uniformity of dosage units, assay, dissolution and dissolution profile tests. The tablets were also evaluated by hardness and friability tests. All analyzed samples were considered suitable in relation to the uniformity of weight, hardness and friability (tablets), disintegration and uniformity of dosage units tests. The compounded capsules were not considered appropriate in relation to the dissolution and dissolution profile tests, demonstrating rapid diltiazem release from the pharmaceutical form, unlike the tablets. Therefore, further studies are required to understand the pharmacokinetic parameters presented by this pharmaceutical form, to establish an appropriate posology and to verify if the very rapid diltiazem hydrochloride release does not lead to an increase in the incidence and severity of drug-related adverse effects. Moreover, another possibility would be to modify the compounded capsule formulation to obtain a similar release to the reference drug.