Rational Design Approach to Develop Amorphous Solid Dispersions with Ternary Architecture

Pharmaceutical industry continues to face an ever-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 (ASDs). This approach often results in adequate oral bioavailability to elicit appropriate therapeutic response in patients. ASDs broadly fall into two categories- binary and ternary systems. Typically, ASDs are simple binary systems which contain the drug and a high molecular weight polymer. The majority of the marketed ASD 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 ASD spray-dried particle (true ternary ASD) or externally in the tablet blend (pseudo ternary ASD). Even though ternary ASD systems can provide significant advantage over the binary ASD systems in terms of physical stability and dissolution performance, very few marketed products belong to this category. The reluctance to use ternary ASDs is 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 ASD matrix or externally (in internal or external phase of the tablet). Moreover, addition of a ternary component in the tablet blend can impact the compression/compaction properties of the blend during tablet manufacturing. This in combination with general lack of research centered around downstream processing of ASDs also hampers its full utilization in pharmaceutical industry. There is a therefore need for greater understanding about whether addition of a ternary component in the formulation as excipient would be sufficient or does it really need to be a true ternary system. Furthermore, systematic understanding around addition of a ternary component in the tablet blend to be compressed is warranted. The goal of this research project is to establish a rational design approach to develop ASDs with ternary architecture. A rational design approach will be established by exploring ASDs with different ternary architecture for enhanced performance. In addition, ternary architecture will be explored as a tool to expand the formulation space for ASDs. Ultimately, this will facilitate wider application of ternary ASD systems in industrial settings.