New taste-masking technologies could increase patient compliance and improve production processes
Hermes Pharma, an expert in user-friendly solid oral dosage forms, has begun a joint research project to develop new pharmaceutical formulations and design manufacturing processes accordingly. The company has selected three partners for this project: INNOJET Herbert Hüttlin; the Research Center Pharmaceutical Engineering GmbH (RCPE); and Karl Franzens University Graz.
INNOJET Herbert Hüttlin will be supporting the project with its technical expertise in coating and granulation of solid substances, and providing an INNOJET VENTILUS Fluid Bed System. The latter has already been pre-installed with a hot melt unit. As a non-university research organisation, the RCPE will be providing technical knowledge related to pharmaceutical process and product development, and Karl Franzens University Graz will be supporting the development of new formulations with scientific know-how.
The scope of the project includes developing new approaches to masking the unpleasant taste and smell of APIs that patients often experience when pharmaceuticals dissolve in the mouth. The four partners plan to develop new technologies to coat APIs with lipids and simultaneously overcome the drawbacks of conventional production processes.
The research spans formulation development to the design and implementation of new production processes. There will be a special focus will be on achieving greater efficiency through shorter processing times by developing techniques that eliminate the use of solvents, and by increasing yields.
Coating with polymethacrylate or with modified cellulose is state-of-the-art in today’s pharma industry, but this requires an enormous amount of solvents to be used, but only for processing purposes. The coating of active agent particles with lipids as part of the hot melt coating process is a less costly and more innovative approach to masking the unpleasant taste inherent in APIs. Because solvents are not needed, process cycle times are shortened and subcoating of particles or tablets for isolating purposes becomes redundant.
However, coating with lipids presents other challenges. According to Professor Dr Andreas Zimmer of the Institute for Pharmaceutical Sciences of the University of Graz (Austria), such coatings are often associated with release and stability problems, as during shelf life unwanted changes in polymorphic form can occur. The characterisation of lipids and stability projection are therefore prerequisites for the successful development of pharmaceuticals that incorporate unpleasant substances and dissolve in the mouth.
‘The goal of the research project is to obtain a basic understanding of the crystallisation processes during coating and storage of the final products,’ said Dr Sharareh Salar-Behzadi, senior researcher at the RCPE. ‘As a result, we will be able to predict polymorphic changes better and develop formulations that guarantee not only the required release profile but also effective taste masking over the entire shelf life of the product.’
In addition to highly product-oriented research, the team aims to concentrate on the implementation of new technical processes in production. At the onset of the research project, the selection of the most suitable process technologies was undertaken to facilitate scale-up of the formulation. Part of this technology selection involved the development of a PAT (Process Analytical Technology) solution for direct in-process measurement of critical product attributes.
In conjunction with PAT, the development of a solution is being considered which provides direct real-time information about the chemical composition of the product, for example, the coating layer thickness or water content. It is expected that critical process and quality attributes such as the duration of the process, temperature, spray and release rates could then be predicted more accurately.
The concept of Quality by Design (QbD) will serve as the link between product and process development. Appropriate process technologies will be embedded early to produce high quality pharmaceutical products profitably. The researchers plan to take production process steps into account, even in the product development phase. The partners aim to substitute to a large extent post-production quality control and analytics for in-process measurements with corresponding process control, and expect to obtain related cost savings.
The research project will be carried out by the partner specialists in Graz at the RCPE and at the Karl Franzens University. The initial findings are expected in mid 2013.