A carregar...
Publicação
Research and galenic development of prolonged-release tablets of a decongestant drug
| Nome: | Descrição: | Tamanho: | Formato: | |
|---|---|---|---|---|
| 1.23 MB | Adobe PDF |
Orientador(es)
Resumo(s)
As formas farmacêuticas orais de libertação controlada apresentam diversas vantagens incluindo o decréscimo de flutuações na concentração dos fármacos, redução na frequência da toma de doses e aumento da compliance por parte do utente. Estas têm sido usadas com diversas substâncias ativas incluindo descongestionantes. Estes tipos de fármacos podem ser usados no tratamento sintomático da rinite alérgica e da constipação e são comumente comercializados em associação com outros fármacos nomeadamente anti-histamínicos. O objetivo deste trabalho foi o de desenvolver uma formulação apropriada e obter comprimidos de um fármaco descongestionante de libertação prolongada durante 24 horas com um perfil de dissolução semelhante a um medicamento de referência usando sistemas matriciais. Pretende-se que estes comprimidos sejam mais tarde revestidos com uma camada de libertação imediata de um anti-histamínico. Para obter isto, o Método SeDeM foi usado para estudar as propriedades físicas do fármaco, identificar as suas limitações e selecionar os excipientes certos para produzir formulações com propriedades de deslizamento aceitáveis para serem comprimidas. Os materiais formadores de matrizes usados foram etilcelulose (EC), óleos vegetais hidrogenados (HVOs) e hidroxipropilmetilcelulose (HPMC). Os comprimidos foram obtidos por compressão direta ou por granulação por via húmida seguida de compressão; e a caracterização de parâmetros críticos como a uniformidade de massa dureza e friabilidade foi realizada. A libertação do fármaco das matrizes foi medida baseada no ensaio de dissolução da Farmacopeia Europeia usando o aparelho 2. Os lotes produzidos por compressão direta mostraram resultados promissores com uma libertação prolongada do fármaco durante cerca de 14 horas. No entanto, apresentaram problemas de heterogeneidade entre comprimidos o que levou a descartar este método de produção. Os lotes de granulação por via húmida alcançaram apenas uma libertação prolongada do fármaco durante 8 horas. Verificou-se que as formulações com baixas percentagens de HPMC obtiveram os piores resultados mesmo na presença de EC e HVOs em concentrações maiores. Os melhores resultados foram obtidos com combinações destes três excipientes. Conclui-se que a HPMC é essencial para o controlo da libertação do fármaco e que a adição de HVOs é benéfica. Trabalhos futuros são ainda necessários para otimizar as formulações e os processos de fabrico para atingir a libertação desejada do fármaco durante um período de 24 horas.
Controlled release oral dosage forms have many advantages including decreased fluctuations of drug concentrations, reduction in dosing frequency and enhanced patient compliance. They have been used with multiple active ingredients including decongestants. These types of drugs can be used in the symptomatic treatment of allergic rhinitis and the in common cold and they are often commercialized as an association with other APIs namely antihistamines. The purpose of this study was to develop a suitable formulation and obtain prolonged release tablets of a decongestant drug over 24 hours with a similar dissolution profile as a reference medicine using matrix forming agents. These tablets are planned to later receive a coating layer with an immediate release of an antihistamine. To achieve this, the SeDeM Method was used to study the physical properties of this drug, identify its limitations and select the right excipients to produce an appropriate formulation with acceptable flow properties to be compressed. The matrix forming agents used were, ethylcellulose (EC), hydrogenated vegetable oils (HVOs) and hydroxypropyl methylcellulose (HPMC). The tablets were obtained either by direct compression or wet granulation followed by compression; and the characterization of critical parameters such as uniformity of mass, hardness and friability was assessed. The release of the drug from the matrices was measured based on European Pharmacopeia’s dissolution assay using apparatus 2. The direct compression batches showed promising results with a prolonged release of the API of approximately 14 hours. However, they presented problems in tablet homogeneity which led to the abandonment of this type of process. The wet granulation batches achieved only a prolonged release of the drug over 8 hours. It was found that formulations with low percentages of HPMC had the worst results, even when EC and HVOs were present in higher concentrations. The best results were achieved with a combination of these three excipients. It was concluded that HPMC is essential to control the release of this drug and the addition of HVOs was beneficial. Future work is still needed to optimize the formulations and manufacturing processes in order to accomplish the desired release of the drug over a period of 24 hours.
Controlled release oral dosage forms have many advantages including decreased fluctuations of drug concentrations, reduction in dosing frequency and enhanced patient compliance. They have been used with multiple active ingredients including decongestants. These types of drugs can be used in the symptomatic treatment of allergic rhinitis and the in common cold and they are often commercialized as an association with other APIs namely antihistamines. The purpose of this study was to develop a suitable formulation and obtain prolonged release tablets of a decongestant drug over 24 hours with a similar dissolution profile as a reference medicine using matrix forming agents. These tablets are planned to later receive a coating layer with an immediate release of an antihistamine. To achieve this, the SeDeM Method was used to study the physical properties of this drug, identify its limitations and select the right excipients to produce an appropriate formulation with acceptable flow properties to be compressed. The matrix forming agents used were, ethylcellulose (EC), hydrogenated vegetable oils (HVOs) and hydroxypropyl methylcellulose (HPMC). The tablets were obtained either by direct compression or wet granulation followed by compression; and the characterization of critical parameters such as uniformity of mass, hardness and friability was assessed. The release of the drug from the matrices was measured based on European Pharmacopeia’s dissolution assay using apparatus 2. The direct compression batches showed promising results with a prolonged release of the API of approximately 14 hours. However, they presented problems in tablet homogeneity which led to the abandonment of this type of process. The wet granulation batches achieved only a prolonged release of the drug over 8 hours. It was found that formulations with low percentages of HPMC had the worst results, even when EC and HVOs were present in higher concentrations. The best results were achieved with a combination of these three excipients. It was concluded that HPMC is essential to control the release of this drug and the addition of HVOs was beneficial. Future work is still needed to optimize the formulations and manufacturing processes in order to accomplish the desired release of the drug over a period of 24 hours.
Descrição
Trabalho Final de Mestrado Integrado, Ciências Farmacêuticas, Universidade de Lisboa, Faculdade de Farmácia, 2019
Palavras-chave
Descongestionante Desenvolvimento galénico Comprimidos de libertação modificada Sistemas matriciais Método SeDeM Mestrado Integrado - 2019