Os transferossomas como sistemas de veiculação do ibuprofeno para administração transdérmica
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2021
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patologias, como a dor e a inflamação, representa uma elevada percentagem da
utilização de medicamentos em todo o mundo. Apesar da eficácia demonstrada, os
AINES não seletivos, como o ibuprofeno, estão habitualmente associados a efeitos
adversos que conferem um risco à sua utilização crónica. A pele surge então como
alternativa para a administração de AINES, contudo, a veiculação transcutânea está
limitada pela reduzida capacidade de permeação dos compostos terapêuticos através da
barreira cutânea. De forma a solucionar este problema, têm vindo a surgir várias
abordagens nanotecnológicas, que favorecem a veiculação mais segura e eficaz dos
compostos bioativos através da pele.
Tendo isto em mente, o principal objetivo desta dissertação foi o desenvolvimento
e otimização de uma formulação transferossomal de ibuprofeno de sódio para
administração transdérmica. Inicialmente, foram realizados estudos de pré-formulação
para se caraterizarem as propriedades espectrofotométricas do ibuprofeno de sódio e a
sua solubilidade aquosa. De seguida, foram realizados estudos preliminares no sentido de
se selecionar a composição qualitativa e quantitativa dos transferossomas a desenvolver.
Por último, procedeu-se à otimização da formulação com recurso a um desenho fatorial
do tipo Box-Behnken (BBD). Para tal, foram realizados estudos que consistiram na
avaliação do impacto da concentração lipídica, do rácio de ativadores de superfície (AS)
e do tempo de sonicação no tamanho, índice de polidispersão (PDI) e potencial zeta (PZ)
dos transferossomas. Com base na análise estatística dos dados obtidos, definiu-se então
a formulação ótima com base nos critérios desejáveis pré-definidos para o tamanho, o
PDI e o PZ dos transferossomas.
A formulação transferossomal otimizada apresentou propriedades físico-químicas
promissoras: 115 ± 2 nm (tamanho), 0,19 ± 0,02 (PDI) e 0,1 ± 0,4 mV (PZ), em linha
com as previsões teóricas do BBD, sendo assim possível validar o desenho experimental
implementado neste estudo. Ainda que haja ainda espaço para melhor otimizar a
formulação transferossomal obtida, os resultados deste trabalho representam um grande
avanço quanto à veiculação transdérmica do ibuprofeno de sódio.
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of various disorders, such as pain and inflammation, accounts for a high percentage of drug use worldwide. Despite their demonstrated efficacy, non-selective NSAIDs, such as ibuprofen, are commonly associated with adverse effects that pose a risk to their chronic use. The skin then emerges as an alternative route for the administration of NSAIDs, however, transcutaneous delivery is limited by the reduced ability of therapeutic compounds to permeate through the skin barrier. With the intention of overcome this issue, many nanotechnological procedures have been emerging, which favor safer and more effective delivery of bioactive compounds through the skin. Having this in mind, the principal objective of this dissertation was the development and optimization of a transfersomal formulation of ibuprofen sodium for transdermal administration. Initially, pre-formulation studies were performed to characterize the spectrophotometric properties of ibuprofen sodium and its aqueous solubility. Then, preliminary studies were performed to select the qualitative and quantitative composition of the transfersomes to be developed. Finally, the formulation was optimized using a Box-Behnken factorial design (BBD). To this end, studies were conducted to evaluate the impact of lipid concentration, the ratio of edge activators (EA), and sonication time on the size, polydispersity index (PDI), and zeta potential (PZ) of the transfersomes. Based on the statistical analysis of the obtained data, the optimal formulation was then defined based on the predefined desirable criteria for the size, PDI and PZ of the transferosomes. The optimized transfersomal formulation showed promising physicochemical properties: 115 ± 2 nm (size), 0.19 ± 0.02 (PDI) and 0.1 ± 0.4 mV (PZ), in line with the theoretical BBD predictions, thus it was possible to validate the experimental design implemented in this study. Although there is still room to better optimize the obtained transfersomal formulation, the results of this work represent a great advance regarding the transcutaneous delivery of ibuprofen sodium.
The use of nonsteroidal anti-inflammatory drugs (NSAIDs) for the treatment of various disorders, such as pain and inflammation, accounts for a high percentage of drug use worldwide. Despite their demonstrated efficacy, non-selective NSAIDs, such as ibuprofen, are commonly associated with adverse effects that pose a risk to their chronic use. The skin then emerges as an alternative route for the administration of NSAIDs, however, transcutaneous delivery is limited by the reduced ability of therapeutic compounds to permeate through the skin barrier. With the intention of overcome this issue, many nanotechnological procedures have been emerging, which favor safer and more effective delivery of bioactive compounds through the skin. Having this in mind, the principal objective of this dissertation was the development and optimization of a transfersomal formulation of ibuprofen sodium for transdermal administration. Initially, pre-formulation studies were performed to characterize the spectrophotometric properties of ibuprofen sodium and its aqueous solubility. Then, preliminary studies were performed to select the qualitative and quantitative composition of the transfersomes to be developed. Finally, the formulation was optimized using a Box-Behnken factorial design (BBD). To this end, studies were conducted to evaluate the impact of lipid concentration, the ratio of edge activators (EA), and sonication time on the size, polydispersity index (PDI), and zeta potential (PZ) of the transfersomes. Based on the statistical analysis of the obtained data, the optimal formulation was then defined based on the predefined desirable criteria for the size, PDI and PZ of the transferosomes. The optimized transfersomal formulation showed promising physicochemical properties: 115 ± 2 nm (size), 0.19 ± 0.02 (PDI) and 0.1 ± 0.4 mV (PZ), in line with the theoretical BBD predictions, thus it was possible to validate the experimental design implemented in this study. Although there is still room to better optimize the obtained transfersomal formulation, the results of this work represent a great advance regarding the transcutaneous delivery of ibuprofen sodium.
Descrição
Orientação: Maria Catarina Leite
Palavras-chave
MESTRADO INTEGRADO EM CIÊNCIAS FARMACÊUTICAS, CIÊNCIAS FARMACÊUTICAS, NANOTECNOLOGIA, SISTEMAS DE LIBERTAÇÃO DE MEDICAMENTOS, PHARMACEUTICAL SCIENCES, DRUG DELIVERY SYSTEMS, NANOTECHNOLOGY, ANTI-INFLAMATORIOS NÃO ESTEROIDES, NONSTEROIDAL ANTI-INFLAMMATORY DRUGS