Desenvolvimento e otimização de método analítico por Analytical Quality by Design (AQbD) para determinação de teor do produto acabado Succinato de Solifenacina
Data
2021-12-15
Autores
Diego, Giovanna Cristina Marcelino [UNIFESP]
Orientadores
Calixto, Leandro Augusto [UNIFESP]
Tipo
Trabalho de conclusão de curso de graduação
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O Guia Q14 do ICH surge com o propósito de revisar o guia Q2 (R1) e complementar os guias Q8(R2) a Q12, visando adotar os princípios do QbD (Quality by Design) e aplicar no desenvolvimento e validação de métodos analíticos, denominado AQbD (Analytical Quality by Design). Essa ferramenta ao contrário do desenvolvimento de métodos clássico, adota uma abordagem baseada em análise de riscos que gera uma maior compreensão do procedimento analítico e pode criar a base para uma ciência mais sólida e eficiente, pois permite a melhoria contínua ao longo do ciclo de vida do produto e do método analítico, promovendo o desenvolvimento de métodos mais robustos. Além disso, sua implementação visa reduzir resultados fora da especificação, melhorar o desempenho do processo e obter maior flexibilidade regulatória pois permite operar dentro de uma região extremamente confiável e robusta, conhecida como MODR (Method Operable Design Region). A MODR estabelece controles de método significativos uma vez que qualquer alteração dentro dessa região não configura uma alteração de método. Sendo assim, foi desenvolvido um método analítico por AQbD capaz de determinar o teor do produto Succinato de Solifenacina 10 mg. O Succinato de Solifenacina é comercializado sob a forma de comprimido revestido e está disponível nas dosagens de 5 mg e 10 mg. Ele é indicado para o alívio dos sintomas de frequência urinária, incontinência urinária ou urgência associados com uma bexiga hiperativa, pois atua como um antagonista competitivo dos receptores muscarínicos com seletividade maior para a bexiga urinária que para as glândulas salivares in vivo. Receptores muscarínicos têm um papel importante em várias funções principais mediadas colinergicamente, incluindo contrações da musculatura lisa da bexiga urinária e estimulação da secreção salivar. Para a primeira etapa dos experimentos, foi realizada uma triagem utilizando o delineamento de Plackett-Burman com 8 fatores e 12 experimentos. Seguiu-se para a otimização com o delineamento de composto central com 3 fatores e 20 experimentos. As condições definidas como ideais foram: coluna cromatográfica Eclipse XDB C18 (150 mm x 4,6 mm x 5 μm) usando a técnica de cromatografia líquida de alta eficiência (CLAE) em fase reversa, com eluição isocrática e fase móvel composta por solução de fosfato de sódio monobásico 20 mM contendo 0,1% Trietilamina em pH 3,0 ± 0,1 ajustado com ácido fosfórico 85% : Acetonitrila (76:24), detecção em 225 nm, vazão de 1,3 mL/min e volume de injeção de 10μL. Após a definição do método, foi realizada uma análise de risco e com base nos resultados, foi proposto a melhoria contínua possibilitando identificar e prevenir as possíveis falhas do método analítico. O método analítico é confiável e permite quantificar o ativo Succinato de Solifenacina em produto acabado com seletividade adequada.
ICH Guide Q14 appears with the purpose of revising guide Q2 (R1) and complementing guides Q8 (R2) to Q12, adopting the principles of QbD (Quality by Design) and applying in the development and validation of analytical methods, called AQbD (Analytical Quality by Design). This tool, unlike classical method development, adopts an approach based on risk analysis that generates a greater understanding of the analytical procedure and creates a basis for a more solid and efficient science, as it allows continuous improvement throughout the product and analytical method’s lifecycles, promoting the development of more robust methods. In addition, its implementation aims to reduce results out of specification, improve process performance and obtain greater regulatory flexibility as it allows operating within an extremely reliable and robust region, known as MODR (Method Operable Design Region). The MODR establishes significant method controls since any change within that region does not constitute a method change. Therefore, an analytical method capable of determining the content of the product Solifenacin Succinate 10mg was developed by AQbD. Solifenacin Succinate is commercialized as a coated tablet and is available in dosages of 5 mg and 10 mg. It is indicated for the relief of symptoms of urinary frequency, urinary incontinence, or urgency associated with an overactive bladder, as it acts as a specific muscarinic receptor antagonist with greater selectivity for the urinary bladder than for the salivary glands in vivo. Muscarinic receptors play an important role in several major cholinergically mediated functions, including urinary bladder smooth muscle contractions and stimulation of salivary secretion. For the first stage of the experiments, a screening was performed using the Plackett-Burman design with 8 factors and 12 experiments. This was followed by optimization with the central composite design with 3 factors and 20 experiments. The conditions defined as ideal were: Eclipse XDB C18 chromatographic column (150 mm x 4.6 mm x 5 μm) using high performance liquid chromatography (HPLC) in reversed phase technique, with isocratic elution and mobile phase composed of monobasic sodium phosphate solution 20 mM containing 0.1% Triethylamine at pH 3.0 ± 0.1 adjusted with 85% phosphoric acid: Acetonitrile (76:24), detection at 225 nm, flow rate of 1.3 mL/min and injection volume of 10 μL. After defining the method, a risk analysis was carried out and based on the results, continuous improvement was proposed, allowing to identify and prevent possible failures of the analytical method. The analytical method is reliable and allows to quantify the Solifenacin Succinate asset in a finished product with adequate selectivity.
ICH Guide Q14 appears with the purpose of revising guide Q2 (R1) and complementing guides Q8 (R2) to Q12, adopting the principles of QbD (Quality by Design) and applying in the development and validation of analytical methods, called AQbD (Analytical Quality by Design). This tool, unlike classical method development, adopts an approach based on risk analysis that generates a greater understanding of the analytical procedure and creates a basis for a more solid and efficient science, as it allows continuous improvement throughout the product and analytical method’s lifecycles, promoting the development of more robust methods. In addition, its implementation aims to reduce results out of specification, improve process performance and obtain greater regulatory flexibility as it allows operating within an extremely reliable and robust region, known as MODR (Method Operable Design Region). The MODR establishes significant method controls since any change within that region does not constitute a method change. Therefore, an analytical method capable of determining the content of the product Solifenacin Succinate 10mg was developed by AQbD. Solifenacin Succinate is commercialized as a coated tablet and is available in dosages of 5 mg and 10 mg. It is indicated for the relief of symptoms of urinary frequency, urinary incontinence, or urgency associated with an overactive bladder, as it acts as a specific muscarinic receptor antagonist with greater selectivity for the urinary bladder than for the salivary glands in vivo. Muscarinic receptors play an important role in several major cholinergically mediated functions, including urinary bladder smooth muscle contractions and stimulation of salivary secretion. For the first stage of the experiments, a screening was performed using the Plackett-Burman design with 8 factors and 12 experiments. This was followed by optimization with the central composite design with 3 factors and 20 experiments. The conditions defined as ideal were: Eclipse XDB C18 chromatographic column (150 mm x 4.6 mm x 5 μm) using high performance liquid chromatography (HPLC) in reversed phase technique, with isocratic elution and mobile phase composed of monobasic sodium phosphate solution 20 mM containing 0.1% Triethylamine at pH 3.0 ± 0.1 adjusted with 85% phosphoric acid: Acetonitrile (76:24), detection at 225 nm, flow rate of 1.3 mL/min and injection volume of 10 μL. After defining the method, a risk analysis was carried out and based on the results, continuous improvement was proposed, allowing to identify and prevent possible failures of the analytical method. The analytical method is reliable and allows to quantify the Solifenacin Succinate asset in a finished product with adequate selectivity.
Descrição
Citação
Diego, Giovanna Cristina Marcelino. Desenvolvimento e otimização de método analítico por Analytical Quality by Design (AQbD) para determinação de teor do produto acabado Succinato de Solifenacina. 2021. 79 f. Trabalho de Conclusão de Curso - Instituto de Ciências Ambientais, Químicas e Farmacêuticas da Universidade Federal de São Paulo, Diadema, 2021.