The transition from a conventional batch process to a continuous process is highly actual topic and challenging task for the pharmaceutical industry. The dissertation of pharmacist Krista Taipale-Kovalainen, at the University of Eastern Finland, studied the suitability of a continuous manufacturing process with different configurations and direct-compression and dry-granulated tablet compositions. The intention of this present thesis was to increase knowledge about some known challenges in order to help pharmaceutical industry to evaluate adoption of continuous manufacturing technology. The feasibility and flexibility of the specific continuous manufacturing process line was demonstrated, allowing it to be modified into different configurations and formulations without encountering any significant quality issues.
In order to gather comprehensive information of the usability and effectiveness of a novel continuous manufacturing process line, several different set–up configurations (top-down and horizontal) were studied with direct compressible paracetamol and dry granulated ketoprofen formulations in three investigations. The impact of lubricant-based parameters on tablet quality properties was investigated in all studies. Furthermore, some effects of formulation and manufacturing process design on product quality were examined and assessed.
The aim was to devise robust and stable continuous manufacturing process settings, by exploring the design space (DS) after an investigation of the lubrication-based parameters influencing the continuous direct compression tableting of high dose tablets. The process parameters did not affect the quality of the tablet properties; in contrast, formulation parameters exerted a major influence on the properties of the end product. The design space created showed that this type of continuous manufacturing process line was suitable for producing high dose direct compressible paracetamol tablets, which possessed a predetermined quality.
Furthermore the study determine whether intentional (e.g. overnight hold time, product concentration change) and unintentional (e.g. equipment or software failures) deviations, could affect the critical quality attributes (CQA's) of the final product, and to create a deviation document which would reveal the changes that had occurred in the product concentration during the runs. In this study, it was shown that it was possible to produce tablets with a constant quality with our set-up consisting of several unit operations. However, the set-up had to be very carefully designed and controlled to ensure process stability.
The aim was to demonstrate the feasibility of converting of a high-shear wet granulation (HSWG) batch process to a continuous dry granulation (DG) process without any significant formulation changes, by comparing the critical quality attributes (CQA´s) of the granules and tablet products between these two processes. The results demonstrated the possibilities to convert a batch based HSWG process to a continuous DG process by adopting a flexible and effective approach, thus representing a changing towards a more modern manufacturing process.
Krista Taipale-Kovalainen's dissertation Impact of formulation and process design on tablet quality in continuous manufacturing will be examined at the Faculty of Health Sciences of the University of Eastern Finland on 8 June 2021, starting at 12 noon. The opponent will be Docent Mia Siven from the University of Helsinki and the custos will be Professor Ossi Korhonen from the University of Eastern Finland.