Publicação
Continuous feeding and mixing in continuous tablet manufacturing : measuring system responses to parameter and material changes and implementation of NIR sphere
| Resumo: | Continuous manufacturing is an advantageous choice in many industries, including the pharmaceutical. Its main advantages are better controllability, and, for sufficiently large volumes, lower manufacturing costs by decreased footprint and labor. Since the inception of the process analytical technology initiative (PAT), and more recently, the quality-by-design (QbD) initiative, significant efforts in designing new manufacturing strategies for the pharma industry are underway. Continuous mixing is important in many processes in pharmaceutical manufacturing, including some obvious ones such as API and lubricant mixing, and some less apparent, such as wet granulation, coating, extrusion, and drying, where mixing often plays a critical role. In this study, NIR spectroscopy is used to further understand a novel continuous mixing process. This new method is used to monitor the concentration of paracetamol blends that range from 30 to 70% (w/w). An experimental design was performed to define a set of runs in order to identify the critical process parameters and evaluate their impact on the critical quality attributes such as the homogeneity of the powder blend produced in the in-line mixer. The in-line mixer used was the Hosokawa Modulomix. The mixing process was monitored by an near infrared spectral camera aided by an integration sphere with an innovative design, attached to the mixer’s outlet port. The process parameters evaluated and their respective range were: mixer speed (300-1500 rpm), total feed rate (5-15 kg/h), inlet port (A or B) and excipient type (dibasic calcium phosphate or paracetamol). All process variables were kept constant throughout the experiments, and whilst maintaining the total feed rate constant, step changes to the paracetamol concentration were introduced at different time points. These were meant to stimulate the system and allowed for monitoring of system mixing performance with alterning setpoints for a wide range of settings, and for determination of the mixer’s mean residence time. The NIR spectral camera was able to operate, through the integration sphere’s innovative design, with multi-point signal acquisition for a good representative analysis of the flowing powder. The mixer speed was revealed to be the most important critical process parameter. Mixture performance was determined via the powder blend’s relative standard deviation (RSD), and results revealed that powder homogeneity was very good under all experimental conditions, having the RSD values always remained under 5% RSD. |
|---|---|
| Autores principais: | Canas, André João Nascimento |
| Assunto: | Chemometrics Continuous manufacturing Continuous mixing Near-infrared spectroscopy Powder blending Teses de mestrado - 2017 |
| Ano: | 2017 |
| País: | Portugal |
| Tipo de documento: | dissertação de mestrado |
| Tipo de acesso: | acesso aberto |
| Instituição associada: | Universidade de Lisboa |
| Idioma: | inglês |
| Origem: | Repositório da Universidade de Lisboa |
| Resumo: | Continuous manufacturing is an advantageous choice in many industries, including the pharmaceutical. Its main advantages are better controllability, and, for sufficiently large volumes, lower manufacturing costs by decreased footprint and labor. Since the inception of the process analytical technology initiative (PAT), and more recently, the quality-by-design (QbD) initiative, significant efforts in designing new manufacturing strategies for the pharma industry are underway. Continuous mixing is important in many processes in pharmaceutical manufacturing, including some obvious ones such as API and lubricant mixing, and some less apparent, such as wet granulation, coating, extrusion, and drying, where mixing often plays a critical role. In this study, NIR spectroscopy is used to further understand a novel continuous mixing process. This new method is used to monitor the concentration of paracetamol blends that range from 30 to 70% (w/w). An experimental design was performed to define a set of runs in order to identify the critical process parameters and evaluate their impact on the critical quality attributes such as the homogeneity of the powder blend produced in the in-line mixer. The in-line mixer used was the Hosokawa Modulomix. The mixing process was monitored by an near infrared spectral camera aided by an integration sphere with an innovative design, attached to the mixer’s outlet port. The process parameters evaluated and their respective range were: mixer speed (300-1500 rpm), total feed rate (5-15 kg/h), inlet port (A or B) and excipient type (dibasic calcium phosphate or paracetamol). All process variables were kept constant throughout the experiments, and whilst maintaining the total feed rate constant, step changes to the paracetamol concentration were introduced at different time points. These were meant to stimulate the system and allowed for monitoring of system mixing performance with alterning setpoints for a wide range of settings, and for determination of the mixer’s mean residence time. The NIR spectral camera was able to operate, through the integration sphere’s innovative design, with multi-point signal acquisition for a good representative analysis of the flowing powder. The mixer speed was revealed to be the most important critical process parameter. Mixture performance was determined via the powder blend’s relative standard deviation (RSD), and results revealed that powder homogeneity was very good under all experimental conditions, having the RSD values always remained under 5% RSD. |
|---|