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Development of gastroretentive systems based on osmotically driven expansion
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Muitos dos fármacos desenvolvidos são administrados por via oral, contudo as formas
de libertação oral convencional apresentam como desvantagem a fraca absorção. A
estratégia de retenção de fármacos no estômago tem sido estudada para ultrapassar esta
dificuldade. Neste trabalho, foi desenvolvido um sistema de libertação prolongada,
baseado na Tecnologia Geomatrix®. Este sistema é composto por um comprimido que
possui uma matriz hidrofílica, a qual se encontra rodeada por uma ou duas camadas
poliméricas constituídas por hidroxipropilmetilcelulose ou etilcelulose em diferentes
quantidades (50, 80 ou 100 mg) e por uma unidade osmótica constituída por uma
membrana de diálise e um agente osmótico (cloreto de sódio). As membranas de diálise
testadas possuem massas molecular limite (molecular weight cut-off) diferentes e as
quantidades de agente osmótico variam entre 75, 150 e 300 mg. O sistema é constituído
pelo comprimido que é colado à unidade osmótica e depois é inserido numa cápsula. A
cápsula quando em contacto com o fluido gástrico dissolve-se e liberta o sistema no
estômago. As forças osmóticas promovem a expansão da unidade osmótica até
dimensões superiores ao esfíncter pilórico, o que garante a retenção do sistema no
estômago. As camadas de barreira através da restrição da área de superfície do
comprimido, que está em contacto com o meio de dissolução são capazes de modificar
a taxa de expansão da matriz hidrofílica, o que resulta num maior tempo de libertação
da substância ativa. Foi observado que os comprimidos com três camadas quando
comparados com os comprimidos de duas camadas apresentam um tempo de libertação
do cloridrato de metformina (fármaco modelo) superior. Baseado nos resultados
obtidos, foi ainda possível concluir que o sistema ideal deve possuir um mínimo de 80
mg como camada de barreira para cobrir toda a superfície do comprimido e deve ser
formado pela membrana de diálise com uma massa molecular limite de 3500-5000
Dalton, a qual apresenta uma expansão de volume superior em menor tempo quando
comparada com a outra membrana testada. Os resultados obtidos mostram que os
comprimidos com várias camadas ligados às unidades osmóticas são capazes de
garantir uma libertação prolongada do nosso fármaco modelo.
Most of the drugs developed are administered by the oral route in the patients. Otherwise, the conventional oral tablets have some disadvantages such as the poor absorption. To overcome this, the gastroretention strategy has gained attention in the last years. The work developed adopted this strategy and consists in a prolonged release system based on the Geomatrix® Technology. This system is composed by a drug unit, with a hydrophilic matrix core surrounded by one or two polymeric layers constituted by hydroxypropyl methylcellulose or ethyl cellulose. The amounts of the barrier layers were 50, 80 and 100 mg. The system is also composed by an osmotic unit made by a dialysis membrane with a molecular weight cut off 3500-5000 Da or 12000-14000 Da. This membrane has inside an osmotic agent in the quantity of 75, 150 or 300 mg. To assemble the system, the drug unit was glued to the osmotic unit and after that the system was inserted in a capsule. The contact with the gastric fluid will lead to the dissolution of the capsule, which result in the release of the system in the stomach. The osmotic forces led the osmotic unit to expand to dimensions superior to the pylorus sphincter guaranteeing the gastroretention of the system. The barriers layers thought the restriction of the surface area of the tablet, that contacted with the gastric fluid were able to modify the sweeling rate of the hydrophilic matrix. Comparing the triple-layered tablets with the bilayered formulations was observed that the triple-layered tablets presented a higher time of release of the metformin HCl. Based on the results obtained, was possible to conclude that the ideal system must have a minimum of 80 mg of a barrier layer to cover all the surface of the tablet and the osmotic unit must be formed by the dialysis membrane with 3500-5000 Dalton, since this membrane present a higher swelling when compared to the other membrane tested. The results obtained show that multilayered tablets assembled with an osmotic unit were able to guarantee a prolong release of the drug.
Most of the drugs developed are administered by the oral route in the patients. Otherwise, the conventional oral tablets have some disadvantages such as the poor absorption. To overcome this, the gastroretention strategy has gained attention in the last years. The work developed adopted this strategy and consists in a prolonged release system based on the Geomatrix® Technology. This system is composed by a drug unit, with a hydrophilic matrix core surrounded by one or two polymeric layers constituted by hydroxypropyl methylcellulose or ethyl cellulose. The amounts of the barrier layers were 50, 80 and 100 mg. The system is also composed by an osmotic unit made by a dialysis membrane with a molecular weight cut off 3500-5000 Da or 12000-14000 Da. This membrane has inside an osmotic agent in the quantity of 75, 150 or 300 mg. To assemble the system, the drug unit was glued to the osmotic unit and after that the system was inserted in a capsule. The contact with the gastric fluid will lead to the dissolution of the capsule, which result in the release of the system in the stomach. The osmotic forces led the osmotic unit to expand to dimensions superior to the pylorus sphincter guaranteeing the gastroretention of the system. The barriers layers thought the restriction of the surface area of the tablet, that contacted with the gastric fluid were able to modify the sweeling rate of the hydrophilic matrix. Comparing the triple-layered tablets with the bilayered formulations was observed that the triple-layered tablets presented a higher time of release of the metformin HCl. Based on the results obtained, was possible to conclude that the ideal system must have a minimum of 80 mg of a barrier layer to cover all the surface of the tablet and the osmotic unit must be formed by the dialysis membrane with 3500-5000 Dalton, since this membrane present a higher swelling when compared to the other membrane tested. The results obtained show that multilayered tablets assembled with an osmotic unit were able to guarantee a prolong release of the drug.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, 2024, Universidade de Lisboa, Faculdade de Farmácia.
Palavras-chave
Multilayered tablets Gastroretentive system Polymers Prolonged release Osmotic unit Mestrado Integrado - 2024