PhD project: development of a science based design approach to develop amorphous solid dispersions with ternary architecture
Katholieke Universiteit Leuven
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Pharmaceutical industry continues to face a never-existing situation of discovery pipelines churning out poorly water-soluble drugs which inherently suffer from extremely poor solubility and bioavailability. In order to transform these poorly water-soluble drugs into viable drug products, formulators often use approaches such as amorphous solid dispersions (whereby the drug substance is molecularly dispersed in a polymeric carrier matrix). This approach often results in adequate oral bioavailability to elicit appropriate therapeutic response in patients.
Amorphous solid dispersions broadly fall into two categories- binary and ternary systems. Typically, amorphous solid dispersions are simple binary systems which contain the drug and a high molecular weight polymer. The majority of the marketed amorphous solid dispersion products fall in this category. Ternary systems contain a third component in addition to the drug and a high molecular weight polymer. This third component can be a surfactant or another polymer and can be added within the amorphous solid dispersion matrix or externally (in the internal or external phase of the tablet). Even though ternary amorphous solid dispersion systems can provide significant advantage over the binary amorphous solid dispersion systems in terms of physical stability and dissolution performance, very few marketed products belong to this category.
The reluctance to use ternary amorphous solid dispersionsis driven by the complicated solid state and biopharmaceutics when the drug and polymer is mixed with a ternary component.The addition of surfactants can often even have a negative impact on the physical stability. Furthermore, there is a lack of a well-defined approach to select the ternary component and incorporate this in the drug product: within the amorphous solid dispersions matrix or externally (in internal or external phase of the tablet). Moreover, addition of a ternary component in internal or external phase of the tablet could have potential impact on the compression/compaction properties of the solid dispersion during tablet manufacturing.
The goal of this research project is to establish a rational design approach to develop amorphous solid dispersions with ternary architecture. This will facilitate wider application of such ternary systems in industrial settings. A rational design approach will be established by exploring amorphous solid dispersions with different ternary architecture for enhanced performance. In addition, ternary architecture will be explored as a tool to expand the formulation space for amorphous solid dispersions.
This doctoral thesis project presents a unique opportunity to work on the academia-industry interface on a very important and relevant topic.The project will involve but is not limited to application of different manufacturing techniques (e.g. spray-drying, tableting), various analytical techniques (DSC, XRD, IR,TGA, DVS, HPLC), dissolution testing and stability monitoring. The group of prof. Van den Mooter is worldwide recognized for expertise in the field of amorphous materials and solid (molecular) dispersions of poorly soluble drugs. In a recent paper from Zhang et al. (Molecules, 23(2018) 1697) that focused on literature and patents about solid dispersions from 1980 to 2015, the group of prof. Van den Mooter was listed as the top one for average citations per paper. Janssen Pharmaceutica has gained an in-depth scientific know how, practical experience and extensive manufacturing expertise of several solid dispersions (SporanoxTM, IntelenceTM, OlysioTM, IncivoTM). The research scholar will become acquainted with the practical aspects of solid dispersion development and industrial working environment. The learnings from the project have the potential to be immediately applied in industrial settings thereby helping numerous patients.
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