Influência de pressões e viscosidades no tempo de flutuação e na taxa de liberação de comprimidos magnéticos flutuantes avaliados por Biosusceptometria AC
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Data
2021-03-08
Autores
Rodrigues, Gustavo Serafim [UNESP]
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Editor
Universidade Estadual Paulista (Unesp)
Resumo
O desenvolvimento de formas farmacêuticas para liberação controlada de fármacos, como comprimidos, tem aumentado significantemente ao longo dos anos, com o objetivo de se obter um tratamento mais eficaz e de melhor aceitação do paciente. Os sistemas gastrorretensivos, são um tipo de liberação controlada de fármacos, que tem por principal objetivo o aumento do tempo de retenção gástrica (TRG) de formas farmacêuticas sólidas. Dentre os sistemas gastrorretensivos, os sistemas flutuantes ou sistemas controlados dinamicamente são sistemas que apresentam baixa densidade, possuem capacidade suficiente para flutuar sobre o conteúdo gástrico e permanecer flutuando no estômago sem afetar a taxa de esvaziamento gástrico por um período de tempo prolongado. Isso resulta em um aumento do tempo de retenção gástrica (TRG) e um melhor controle na concentração plasmática do fármaco liberado. O emprego de técnicas biomagnéticas, como a Biosusceptometria AC (BAC) para avaliar formas farmacêuticas flutuantes no TGI tem apresentado bons resultados ao longo do tempo. Desta maneira, a proposta deste trabalho consistiu na avaliação do tempo de início de flutuação que vem do termo em inglês (Floating Lag Time- FLT) e a taxa de liberação de comprimidos magnéticos flutuantes de sistemas gastrorretensivos flutuantes magneticamente marcados que promovam a liberação controlada do metronidazol in vitro, aplicando diferentes pressões e viscosidades no meio, simulando diferentes partes do estômago humano em diferentes estados prandiais. Para este estudo, foram preparadas quatro soluções, sendo uma considerada padrão com viscosidade similar à da água (1 mPa.s), e as outras com 50, 120 e 320 mPa.s. Para cada solução foram aplicadas 3 pressões diferentes (atm, 150 e 300 mmHg). Foram avaliados o início do tempo de flutuação (FLT) e a taxa de liberação do metronidazol para meio viscoso, aplicando as diferentes pressões para cada meio. O dispositivo BAC monosensor foi empregado para a avaliação em tempo real do processo de início de flutuação da FFS flutuante a partir de um escaneamento e posteriormente foi feita uma imagem magnética do mesmo. Todas os experimentos foram realizados com as soluções com pH 1,2 e temperatura de 37±0,5 ºC. Os resultados da taxa de liberação do metronidazol e o tempo de início de flutuação (FLT) revelaram que o aumento de pressão não apresentou diferença significativa na taxa de liberação do metronidazol nos diferentes meios, porém aumentou de forma significativa o FLT dos comprimidos, principalmente aplicando a pressão de 300 mmHg. Já as diferentes viscosidades dos meios, apresentaram diferenças significativas na taxa de liberação do metronidazol e no FLT, principalmente para o meio com viscosidade de 320 mPa.s. Esses eventos ocorrem, pois com o aumento da viscosidade, se forma uma camada densa ao redor do comprimido, com isso o fluxo de fluído para o interior do comprimido ocorre de forma mais lenta, resultando no retardo de reação do fluído com o núcleo do comprimido, diminuindo a liberação do fármaco para o meio e consequentemente o tempo de início de flutuação (FLT).
The development of pharmaceutical forms for controlled release of drugs, such as pills, has increased significantly over the years, with the objective of obtaining a more effective treatment and better patient acceptance. Gastroretensive systems are a type of controlled drug release, whose main objective is to increase the gastric retention time (GRT) of solid pharmaceutical forms. Among gastroretensive systems, floating systems or dynamically controlled systems are systems that present low density, have sufficient capacity to float on the gastric contents and remain floating in the stomach without affecting the gastric emptying rate for an extended period of time. This results in an increase in gastric retention time (GRT) and better control of the plasma concentration of the released drug. The use of biomagnetic techniques, such as AC Biosusceptometry (BAC) to evaluate pharmaceutical forms floating in the TGI has shown good 12 results over time. Thus, the purpose of this study was to evaluate the time of onset of flotation that comes from the term in English (Floating Lag Time-FLT) and the release rate of floating magnetic tablets from magnetically marked floating gastroretensive systems that promote the controlled release of the metronidazole in vitro, applying different pressures and viscosities in the medium, simulating different parts of the human stomach in different prandial states. For this study, four solutions were prepared, one being considered standard with viscosity similar to that of water (1 mPa.s), and the others with 50, 120 and 320 mPa.s. For each solution, 3 different pressures were applied (atm, 150 and 300 mmHg). The beginning of the floating time (FLT) and the release rate of metronidazole for viscous medium were evaluated, applying the different pressures for each medium. The monosensor BAC device was used for real-time evaluation of the floating FFS start process from a scan, and subsequently a magnetic image was taken. All experiments were carried out with solutions with pH 1.2 and temperature of 37±0.5 ºC. The results of the metronidazole release rate and the time to onset of fluctuation (FLT) revealed that the pressure increase did not show a significant difference in the metronidazole release rate in different media, but it significantly increased the FLT of the tablets, mainly by applying the pressure of 300 mmHg. However, the different viscosities of the media showed significant differences in the release rate of metronidazole and FLT, especially for the media with a viscosity of 320 mPa.s. These events occur because with the increase in viscosity, a dense layer forms around the tablet, with this the flow of fluid into the tablet occurs more slowly, resulting in a delay in the reaction of the fluid with the tablet core, decreasing the drug release to the medium and consequently the fluctuation onset time (FLT).
The development of pharmaceutical forms for controlled release of drugs, such as pills, has increased significantly over the years, with the objective of obtaining a more effective treatment and better patient acceptance. Gastroretensive systems are a type of controlled drug release, whose main objective is to increase the gastric retention time (GRT) of solid pharmaceutical forms. Among gastroretensive systems, floating systems or dynamically controlled systems are systems that present low density, have sufficient capacity to float on the gastric contents and remain floating in the stomach without affecting the gastric emptying rate for an extended period of time. This results in an increase in gastric retention time (GRT) and better control of the plasma concentration of the released drug. The use of biomagnetic techniques, such as AC Biosusceptometry (BAC) to evaluate pharmaceutical forms floating in the TGI has shown good 12 results over time. Thus, the purpose of this study was to evaluate the time of onset of flotation that comes from the term in English (Floating Lag Time-FLT) and the release rate of floating magnetic tablets from magnetically marked floating gastroretensive systems that promote the controlled release of the metronidazole in vitro, applying different pressures and viscosities in the medium, simulating different parts of the human stomach in different prandial states. For this study, four solutions were prepared, one being considered standard with viscosity similar to that of water (1 mPa.s), and the others with 50, 120 and 320 mPa.s. For each solution, 3 different pressures were applied (atm, 150 and 300 mmHg). The beginning of the floating time (FLT) and the release rate of metronidazole for viscous medium were evaluated, applying the different pressures for each medium. The monosensor BAC device was used for real-time evaluation of the floating FFS start process from a scan, and subsequently a magnetic image was taken. All experiments were carried out with solutions with pH 1.2 and temperature of 37±0.5 ºC. The results of the metronidazole release rate and the time to onset of fluctuation (FLT) revealed that the pressure increase did not show a significant difference in the metronidazole release rate in different media, but it significantly increased the FLT of the tablets, mainly by applying the pressure of 300 mmHg. However, the different viscosities of the media showed significant differences in the release rate of metronidazole and FLT, especially for the media with a viscosity of 320 mPa.s. These events occur because with the increase in viscosity, a dense layer forms around the tablet, with this the flow of fluid into the tablet occurs more slowly, resulting in a delay in the reaction of the fluid with the tablet core, decreasing the drug release to the medium and consequently the fluctuation onset time (FLT).
Descrição
Palavras-chave
Biosusceptometria de corrente alternada (BAC), Sistemas gastrorretensivos, Floating Lag Time (FLT), Comprimidos magnéticos flutuantes, Pressão Intragástrica, Viscosidade, AC Biosusceptometry, Gastroretensive systems,