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Validação de Método Analítico de Dissolução para Quantificação de Substâncias Ativas em Comprimidos
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A presente dissertação visa a validação do método analítico de dissolução de medicamentos, essencial para garantir a sua eficácia e segurança. Os objetivos são validar o método para comprimidos de Paracetamol+Cafeína (500/65 mg) e avaliar os perfis de dissolução de comprimidos revestidos de ciclobenzaprina (10 mg). Para isso foram utilizados métodos experimentais para analisar medicamentos de referência e lotes de desenvolvimento. No caso do Paracetamol+Cafeína, demonstrou-se que o método analítico é específico, linear (20%-120%), exato (recuperação de 95%-105%), repetível (RSD ≤ 3.0%) e preciso entre analistas (RSD ≤ 2.0%). O processo de fabrico foi otimizado, produzindo lotes bioequivalentes ao Panadol Extra®, com dissolução das substâncias ativas superior a 85% em 15 minutos, validando assim a sua classificação como biowaiver de classe I no Sistema BCS e eliminando a necessidade de estudos in vivo. No que respeita à ciclobenzaprina, observou-se que a compressão e o revestimento influenciam a dissolução e que não se conseguiu atingir uma dissolução de 85% nos primeiros 15 minutos. Também os perfis de dissolução do lote piloto diferiram dos do medicamento de referência (fator f2 ≤ 50). Conclui-se que o método de dissolução de Paracetamol+Cafeína foi validado com sucesso, enquanto o desenvolvimento de ciclobenzaprina requer melhorias no processo de fabrico e validação. O estudo abre perspetivas para otimizações contínuas e estudos futuros, incluindo a análise de estabilidade e continuidade de validação de métodos analíticos.
This dissertation aims to validate the analytical method for dissolution of medicines, which is essential for guaranteeing their efficacy and safety. The objectives are to validate the method for Paracetamol+Caffeine tablets (500/65 mg) and to evaluate the dissolution profiles of cyclobenzaprine coated tablets (10 mg). To do this, experimental methods were used to analyse reference drugs and development batches. In the case of Paracetamol+Caffeine, the analytical method was shown to be specific, linear (20%-120%), accurate (95%-105% recovery), repeatable (RSD ≤ 3.0%) and precise between analysts (RSD ≤ 2.0%). The manufacturing process has been optimised, producing batches that are bioequivalent to Panadol Extra®, with dissolution of the active substances exceeding 85% in 15 minutes, thus validating its classification as a class I biowaiver in the BCS System and elimi-nating the need for in vivo studies. Regarding cyclobenzaprine, it was observed that compression and coating influence dissolution and that 85% dissolution was not achieved in the first 15 minutes. The dissolution profiles of the pilot batch also differed from those of the reference medicine (f2 fac-tor ≤ 50). It is concluded that the Paracetamol+Caffeine dissolution method has been successfully validated, while the development of cyclobenzaprine requires improvements in the manufacturing and validation process. This study opens up prospects for continued optimisation and future studies, including stability analysis and continued validation of analytical methods.
This dissertation aims to validate the analytical method for dissolution of medicines, which is essential for guaranteeing their efficacy and safety. The objectives are to validate the method for Paracetamol+Caffeine tablets (500/65 mg) and to evaluate the dissolution profiles of cyclobenzaprine coated tablets (10 mg). To do this, experimental methods were used to analyse reference drugs and development batches. In the case of Paracetamol+Caffeine, the analytical method was shown to be specific, linear (20%-120%), accurate (95%-105% recovery), repeatable (RSD ≤ 3.0%) and precise between analysts (RSD ≤ 2.0%). The manufacturing process has been optimised, producing batches that are bioequivalent to Panadol Extra®, with dissolution of the active substances exceeding 85% in 15 minutes, thus validating its classification as a class I biowaiver in the BCS System and elimi-nating the need for in vivo studies. Regarding cyclobenzaprine, it was observed that compression and coating influence dissolution and that 85% dissolution was not achieved in the first 15 minutes. The dissolution profiles of the pilot batch also differed from those of the reference medicine (f2 fac-tor ≤ 50). It is concluded that the Paracetamol+Caffeine dissolution method has been successfully validated, while the development of cyclobenzaprine requires improvements in the manufacturing and validation process. This study opens up prospects for continued optimisation and future studies, including stability analysis and continued validation of analytical methods.
Descrição
Palavras-chave
ensaio de dissolução validação de método analítico bioequivalência Paracetamol+Cafeína Ciclobenzaprina