Preparation and scale up of extended-release tablets of bromopride

Abstract

Reproducibility of the tablet manufacturing process and control of its pharmaceutics properties depends on the optimization of formulation aspects and process parameters. Computer simulation such as Design of Experiments (DOE) can be used to scale up the production of this formulation, in particular for obtaining sustained-release tablets. Bromopride formulations are marketed in the form of extended-release pellets, which makes the product more expensive and difficult to manufacture. The aim of this study was to formulate new bromopride sustained release formulations as tablets, and to develop mathematical models to standardize the scale up of this formulation, controlling weight and hardness of the tablets during manufacture according to the USP 34 th edition. DOE studies were conducted using Minitab ™ software. Different excipient combinations were evaluated in order to produce bromopride sustained-release matrix tablets. In the scale-up study, data were collected and variations in tableting machine parameters were measured. Data were processed by Minitab ™ software, generating mathematical equations used for prediction of powder compaction behavior, according to the settings of the tableting machine suitable for scale-up purposes. Bromopride matrix tablets with appropriate characteristics for sustained release were developed. The scale-up of the formulation with the most suitable sustained release profile was established by using mathematical models, indicating that the formulation can be a substitute for the pellets currently marketed.Uniterms: Bromopride/extended-release tablets/preparation. Design of experiments. Extended-release tablets/scale up obtention. Direct compression. Tablets/kinetics release.A reprodutibilidade do processo de fabricação de comprimidos e o controle das suas propriedades farmacotécnicas depende da otimização dos aspectos de formulação e dos parâmetros de processo. O planejamento de experimentos como o Desenho de Experimentos (DOE) pode ser utilizado para acelerar a produção desta formulação, em particular, para a obtenção de comprimidos de liberação prolongada. Formulações de bromoprida são comercializadas sob a forma de péletes de liberação prolongada, o que torna o produto caro e de difícil fabricação. O objetivo deste estudo foi preparar novas formulações de bromoprida de liberação prolongada na forma de comprimidos e desenvolver modelos matemáticos visando ao escalonamento destas formulações, controlando o peso e a dureza dos comprimidos durante a fabricação, de acordo com a 34ª Edição da USP. Estudos de DOE foram realizados utilizando o software Minitab™. Diferentes combinações de excipientes foram avaliadas visando à obtenção dos comprimidos de liberação prolongada de bromoprida. No estudo de scale-up, coletaram-se e mediu-se a influência das variações nos parâmetros da máquina de compressão. Processaram-se os dados obtidos pelo software Minitab ™, gerando equações matemáticas aptas para a previsão do comportamento de compactação do pó em escala industrial. Os comprimidos obt...

İlaç Formülasyonu Geliştirilmesinde Deney Tasarımı (DoE) Seçimi ve Kullanımı

“…Benzer şekilde değerlendirildiğinde, üçüncü satırda verilen çalışmada 2 4 tam faktöriyel tasarımı kullanılarak 16 deneme yapılmıştır (21). Ancak tablet sertliği ve tablet ağırlığı değişiminin kalite çıktısı olarak ölçüldüğü bu çalışmada, tüm faktörler sayısal ve ayarlanabilirdir.…”

Development of a Scalable Process of Film-Coated bi-Layer Tablet Containing Sustained-Release Metoprolol Succinate and Immediate-Release Amlodipine Besylate

“…Among various tablet manufacturing techniques, direct compression has been realized as the most practical and cost-effective technique. For this process, tablets are obtained from the mixture of active ingredients and diluents, followed by the addition of lubricants, disintegrants, and finally, by compression of the final mixture [8]. In addition, blending is an important and common manufacturing process for preparing a solid dosage form (i.e., tablets and capsules) of pharmaceutical drugs.…”