Publicação
A quality by design approach on pharmaceutical development of orally disintegrating tablet of Diazepam
| Resumo: | The purpose of this study was to develop an orally disintegrating tablet (ODT) of diazepam, taken Quality by Design (QbD) approach to achieve it. Pharmaceutical development of ODT of diazepam started with the definition of the target quality attributes that it was expected for the final product. These QTPP formed the basis of the CQAs, which were identified consequently and used for all experiments. The experimental part were divided in two parts: drug product development and manufacturing process development. In drug product development study, an initial risk assessment was performed in order to identify the formulation variables that impact the CQAs. A feasibility study was performed and revealed the acceptable compression parameters and the importance of the binder on drug product. The factors identified on risk assessment, type and amount of disintegrant were analyzed and the results indicated crospovidone as the better superdisintegrant, allowing better ODT characteristics. Therefore, crospovidone was used in the next studies. For manufacturing process development, an initial assessment of each unit operation was made using a Fishbone diagram, to identify potential variables of the process impact product quality. A risk assessment was undertaken to identify the process variables (CPPs) that that impact on product quality. The manufacturing process development was conducted in two studies. The first study evaluated impact of the scaling-up on the compression machine, and settled the amount of crospovidone at 30%. A 32 full factorial Design of Experiment (DoE) design was used in the second study in order to understand the relationship between the compression machine speed and compression force with the drug product quality attributes. Results indicated that compression force was the most critical compression process factor affecting hardness, disintegration time, wetting time and dissolution. In summary, it was possible to development an ODT of diazepam through QbD. |
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| Autores principais: | Teixeira, João Filipe Dias |
| Assunto: | Diazepam Medicamento, qualidade Solubilidade Comprimidos |
| Ano: | 2014 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Coimbra |
| Idioma: | inglês |
| Origem: | Estudo Geral - Universidade de Coimbra |
| Resumo: | The purpose of this study was to develop an orally disintegrating tablet (ODT) of diazepam, taken Quality by Design (QbD) approach to achieve it. Pharmaceutical development of ODT of diazepam started with the definition of the target quality attributes that it was expected for the final product. These QTPP formed the basis of the CQAs, which were identified consequently and used for all experiments. The experimental part were divided in two parts: drug product development and manufacturing process development. In drug product development study, an initial risk assessment was performed in order to identify the formulation variables that impact the CQAs. A feasibility study was performed and revealed the acceptable compression parameters and the importance of the binder on drug product. The factors identified on risk assessment, type and amount of disintegrant were analyzed and the results indicated crospovidone as the better superdisintegrant, allowing better ODT characteristics. Therefore, crospovidone was used in the next studies. For manufacturing process development, an initial assessment of each unit operation was made using a Fishbone diagram, to identify potential variables of the process impact product quality. A risk assessment was undertaken to identify the process variables (CPPs) that that impact on product quality. The manufacturing process development was conducted in two studies. The first study evaluated impact of the scaling-up on the compression machine, and settled the amount of crospovidone at 30%. A 32 full factorial Design of Experiment (DoE) design was used in the second study in order to understand the relationship between the compression machine speed and compression force with the drug product quality attributes. Results indicated that compression force was the most critical compression process factor affecting hardness, disintegration time, wetting time and dissolution. In summary, it was possible to development an ODT of diazepam through QbD. |
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