Preparo de misturas de celecoxibe e ciclodextrina para o aumento da solubilidade do fármaco em meio aquoso
Data
2023-01-04
Autores
Escudeiro, Júlia de Souza 
Orientadores
Andréo Filho, Newton
Tipo
Trabalho de conclusão de curso
Título da Revista
ISSN da Revista
Título de Volume
Resumo
O celecoxibe é um anti-inflamatório não esteroide (AINE), classificado como fármaco de classe II, segundo o Sistema de Classificação Biofarmacêutica (SCB), por apresentar baixa solubilidade e alta permeabilidade. A grande utilização de AINEs consagra o grupo de medicamentos mais difundido, sendo uma realidade em todo o mundo. O tema interessa diversos setores e há demanda projetada do setor de pesquisa acadêmica e de indústrias farmacêuticas. É sabido que a solubilidade de um medicamento de via oral estabelece condição prévia de absorção e, assim, se constitui um dos mais importantes impedimentos à eficácia. O presente trabalho, buscou aumentar a solubilidade do celecoxibe, esperando que o mesmo possa estar mais disponível para ser absorvido quando administrado oralmente, possibilitando a administração de doses menores. Testou-se em diferentes pHs a solubilidade do CLX (celecoxibe) tanto em HCl 0,1 mol/L, como em soluções tampão acetato pH 4,5, tampão fosfato pH 6,8 e 7,4 e foi entendido que sua solubilidade é aumentada, conforme mais ácido for o pH. Para fim de obtenção do complexo de inclusão, preparou-se uma amostra proveniente da mistura de um solução alcoólica de celecoxibe e solução hidroalcoólica de βCD e também de HPβCD. As amostras ficaram em repouso, gerando duas fases: a sólida precipitada e a líquida, posteriormente separadas por um processo de filtração. Na fase sólida de cada amostra, foi realizada a evaporação do solvente em estufa e as porções líquidas foram congeladas e liofilizadas. Para cada amostra final obtida, preparou-se alíquotas diluídas em álcool absoluto. Posteriormente, utilizando-se o espectrofotômetro de UV-vis, foram quantificadas em comprimento de onda de 253 nm e através disso calculou-se a concentração de celecoxibe dissolvida em cada uma das quatro amostras, bem como o teor do fármaco, o qual se mostrou mais significativo para a porção sólida contendo CLX:βCD. Em seguida, após a construção da curva analítica de celecoxibe em HCl 0,1 mol/L, se fez ensaio de solubilidade dessa porção mais promissora neste meio. Utilizando-se o espectrofotômetro de UV-vis, foi quantificada em comprimento de onda de 248 nm, permitindo calcular um aumento de solubilidade de 632,47%, em meio ácido (pH 1,20).
Celecoxib is a non-steroidal anti-inflammatory drug (NSAID), classified as a class II drug, according to the Biopharmaceutical Classification System (SCB), due to its low solubility and high permeability. The wide use of NSAIDs enshrines the most widespread group of drugs, being a reality all over the world. The theme is highly interesting for several sectors, and there is expected demand from the academic research sector and pharmaceutical industries. It is known that the solubility of an oral medication establishes a precondition for absorption and, therefore, constitutes one of the most important impediments to efficacy. The present work sought to increase the solubility of celecoxib, hoping that it could be more available to be absorved when administered orally, allowing the administration of smaller doses. The solubility of CLX (celecoxib) was tested for different pHs both in 0.1 mol/L HCl and in acetate pH 4.5, phosphate precursor pH 6.8 and 7.4 solutions, and it was understood that its solubility is increased, as the pH is more acidic. In order to obtain the inclusion complex, a sample was prepared from a mixture of an alcoholic solution of celecoxib and a hydroalcoholic solution of βCD and also of HPβCD. The samples remained at rest, generating two phases: the precipitated solid and the liquid, later separated by a filtration process. In the solid phase of each sample, the solvent was evaporated in an oven and the liquid portions were frozen and lyophilized. For each final sample obtained, aliquots diluted in absolute alcohol were prepared. Subsequently, using the UV-vis spectrophotometer, they were quantified at a wavelength of 253 nm and through this the dissolved celecoxib concentration in each of the four samples was calculated, as well as the drug content, which proved to be more significant for the solid portion containing CLX:βCD. Then, after constructing the analytical curve of celecoxib in 0.1 mol/L HCl, a solubility test was carried out on this most promising portion in this medium. Using the UV-vis spectrophotometer, it was quantified at a wavelength of 248 nm, allowing the calculation of an increase in solubility of 632,47% in an acid medium (pH 1.20).
Celecoxib is a non-steroidal anti-inflammatory drug (NSAID), classified as a class II drug, according to the Biopharmaceutical Classification System (SCB), due to its low solubility and high permeability. The wide use of NSAIDs enshrines the most widespread group of drugs, being a reality all over the world. The theme is highly interesting for several sectors, and there is expected demand from the academic research sector and pharmaceutical industries. It is known that the solubility of an oral medication establishes a precondition for absorption and, therefore, constitutes one of the most important impediments to efficacy. The present work sought to increase the solubility of celecoxib, hoping that it could be more available to be absorved when administered orally, allowing the administration of smaller doses. The solubility of CLX (celecoxib) was tested for different pHs both in 0.1 mol/L HCl and in acetate pH 4.5, phosphate precursor pH 6.8 and 7.4 solutions, and it was understood that its solubility is increased, as the pH is more acidic. In order to obtain the inclusion complex, a sample was prepared from a mixture of an alcoholic solution of celecoxib and a hydroalcoholic solution of βCD and also of HPβCD. The samples remained at rest, generating two phases: the precipitated solid and the liquid, later separated by a filtration process. In the solid phase of each sample, the solvent was evaporated in an oven and the liquid portions were frozen and lyophilized. For each final sample obtained, aliquots diluted in absolute alcohol were prepared. Subsequently, using the UV-vis spectrophotometer, they were quantified at a wavelength of 253 nm and through this the dissolved celecoxib concentration in each of the four samples was calculated, as well as the drug content, which proved to be more significant for the solid portion containing CLX:βCD. Then, after constructing the analytical curve of celecoxib in 0.1 mol/L HCl, a solubility test was carried out on this most promising portion in this medium. Using the UV-vis spectrophotometer, it was quantified at a wavelength of 248 nm, allowing the calculation of an increase in solubility of 632,47% in an acid medium (pH 1.20).