Influência da Motilidade Gastrintestinal no processo de desintegração de comprimidos
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Data
2016-03-04
Autores
Pires, Deivid William [UNESP]
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Universidade Estadual Paulista (Unesp)
Resumo
A via oral de administração de fármacos é seguramente a mais empregada, não apenas pela facilidade de administração, mas também pela adesão do paciente ao tratamento. Dentre as formas de apresentação oral, os comprimidos são os mais utilizados, uma vez que são apresentações bastante seguras e estáveis. Para o desenvolvimento de novas formulações é essencial o conhecimento de parâmetros fisiológicos que possam influenciar no desempenho da forma farmacêutica. É possível supor que parâmetros da atividade motora do trato gastrintestinal podem trazer implicações significativas na biodisponibilidade de fármacos administrados por via oral. A Prucaloprida é um agonista do receptor 4-serotonina com conhecidos efeitos colocinéticos e possíveis efeitos procinéticos, acelerando a propulsão do conteúdo lumial. Assim, estudar o efeito da Prucaloprida no trânsito gastrintestinal se torna importante, já que pode influenciar no processo de desintegração de comprimidos e na biodisponibilidade de um fármaco. O objetivo desse trabalho foi avaliar o efeito da Prucaloprida no Trânsito Gastrintestinal e como esse efeito influi nos processos de desintegração de um comprimido e na biodisponibilidade do Metronidazol (marcador farmacocinético). Foram produzidos lotes de comprimidos contendo 100 mg de metronidazol, com e sem adição de ferrita na formulação, para estudar os fatores de correlação entre os perfis de dissolução, in vitro, e verificar a influência da ferrita no processo de dissolução do fármaco. Cada lote foi avaliado através de testes farmacotécnicos e avaliados segundo o perfil de dissolução. Para os experimentos in vivo, cada voluntário foi submetido a duas fases de estudos, em dias distintos, para avaliar a biodisponibilidade do metronidazol. Os dispositivos BAC multissensor e monossensor foram empregados para a avaliação em tempo real do processo de desintegração do comprimido e avaliar os parâmetros de trânsito no trato gastrintestinal. Os lotes de comprimidos com e sem ferrita tiveram perfis de dissolução significativamente diferentes para concentração dissolvida e eficiência de dissolução, mas apresentaram similaridade segundo o fator f2 proposto por Moore & Flaner, 1996, com variação máxima de 10% entre elas. Nos ensaios in vivo, o efeito do tratamento por prucaloprida provocou significativa redução no TEG e na biodisponibilidade do metronidazol sérico. A Prucaloprida, em dose de 1 mg, apresentou efeitos significativos no Trânsito Gastrintestinal e em parâmetros da biodisponibilidade do Metronidazol (MT), devido a rápida exposição do conteúdo gástrico ao intestino delgado e, dessa forma, alterando significativamente a taxa de absorção do MT.
The oral route of drugs administration is surely the most used, not only for being easily employed, but also due to the patient adhesion. Among them, tablets are the most common, since they present safe and stable features. In order to develop new formulations, it is essential to acknowledge some physiological parameters and their influence on the pharmaceutical form performance. It is possible to speculate that motor activity parameters of the gastrointestinal tract might interfere in the drug availability after oral administration. Prucalopride is a 4-serotonine receptor agonist with known colonkinetic and possible prokinetic effects, which accelerates the luminal content propulsion. Therefore, it is important to study its effects on the gastrointestinal transit, since it might influence the tablet disintegration process and bioavailability. The objective of this study was to assess the Prucalopride effect on the gastrointestinal transit and how it affects the tablet disintegration process and the Metronidazol (pharmacokinetic marker) bioavailability. Tablet batches were produced, 100 mg of Metronidazol, with and without ferrite, in order to study correlation factors between the in vitro dissolution process for each batch. The influence of the ferrite in the drug dissolution process was also evaluated. Each batch was assessed by pharmacokinetic tests and by their dissolution profile. On regards to the in vivo experiment, each volunteer was submitted to a two phase study, in distinct days, in order to assess the metronidazol bioavailability. Both monossensor and multissensor ACB systems were employed in the real time evaluation of the tablet disintegration process and in the assessment on the gastrointestinal transit parameters. Both tablet batches (with and without ferrite) showed different dissolution profiles for dissolved concentration and dissolution efficiency, although some similarities were found in the f2 factor, proposed by Moore & Flaner, 1996, with maximum variation of 10% between them. Regarding the in vivo study, the prucalopride treatment demonstrated a significant reduction effect in the gastric emptying time and in the serum metronidazol bioavailability. The prucalopride, at 1 mg, produced significant effects in the gastrointestinal transit and in the metronidazol bioavailability due to the fast exposure of the gastric content to the small bowel and, therefore, modifying significantly, the metronidazol absorption rate.
The oral route of drugs administration is surely the most used, not only for being easily employed, but also due to the patient adhesion. Among them, tablets are the most common, since they present safe and stable features. In order to develop new formulations, it is essential to acknowledge some physiological parameters and their influence on the pharmaceutical form performance. It is possible to speculate that motor activity parameters of the gastrointestinal tract might interfere in the drug availability after oral administration. Prucalopride is a 4-serotonine receptor agonist with known colonkinetic and possible prokinetic effects, which accelerates the luminal content propulsion. Therefore, it is important to study its effects on the gastrointestinal transit, since it might influence the tablet disintegration process and bioavailability. The objective of this study was to assess the Prucalopride effect on the gastrointestinal transit and how it affects the tablet disintegration process and the Metronidazol (pharmacokinetic marker) bioavailability. Tablet batches were produced, 100 mg of Metronidazol, with and without ferrite, in order to study correlation factors between the in vitro dissolution process for each batch. The influence of the ferrite in the drug dissolution process was also evaluated. Each batch was assessed by pharmacokinetic tests and by their dissolution profile. On regards to the in vivo experiment, each volunteer was submitted to a two phase study, in distinct days, in order to assess the metronidazol bioavailability. Both monossensor and multissensor ACB systems were employed in the real time evaluation of the tablet disintegration process and in the assessment on the gastrointestinal transit parameters. Both tablet batches (with and without ferrite) showed different dissolution profiles for dissolved concentration and dissolution efficiency, although some similarities were found in the f2 factor, proposed by Moore & Flaner, 1996, with maximum variation of 10% between them. Regarding the in vivo study, the prucalopride treatment demonstrated a significant reduction effect in the gastric emptying time and in the serum metronidazol bioavailability. The prucalopride, at 1 mg, produced significant effects in the gastrointestinal transit and in the metronidazol bioavailability due to the fast exposure of the gastric content to the small bowel and, therefore, modifying significantly, the metronidazol absorption rate.
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Palavras-chave
Prucaloprida, Trânsito Gastrintestinal, Biodisponibilidade, Dissolução, Fator de Similaridade, Prucalopride, Gastrointestinal Transit, Bioavailability, Dissolution, Similarity Factor