(189u) Characterization of the Formulation-Process Interaction for Improved Thermal Bonding in the Manufacture of a Novel Ultra-Long Acting Oral Dosage Form

Lyndra Therapeutics is developing an ultra-long acting oral dosage form that reduces pill burden and helps improve patient adherence to medication. The performance requirements associated with achieving extended gastric residence and linear, multi-day drug release are significantly different than those of traditional solid oral dosage forms. Lyndra’s dosage form meets these requirements through the incorporation of multiple specialized layers that are joined together using a unique thermal bonding process. In order to determine the optimal material formulations and process parameters for creating strong thermal bonds, we sought to better understand the behavior of the materials during the bonding process through thermal and rheological analysis.

The thermal bonding process consists of loading the selected layers into a nest in the desired configuration, applying radial pressure such that all interfaces make contact, and subjecting the exposed side of the components to heat. This process takes advantage of the use of the same base polymer throughout all components, promoting material compatibility at component interfaces. Strong thermal bonds are created when polymer chains are heated to the point at which they can flow across the joint interface and intermingle with chains from the adjacent component. Therefore, the melt viscosity, or resistance to flow, is an important material characteristic to analyze in the context of the Lyndra joining process.

The first step to characterizing the joining process was to understand how the key parameters impacted the materials in question. As a proof of concept, we chose to work with two adjacent layers that have substantially different polymer compositions. The temperature reached by each material during the heating process varies because each material has its own absorptive and conductive properties. The process temperatures were measured using thermocouples inserted directly into the materials. The temperatures of the layers were monitored under standard processing conditions, and alternative processing conditions were also characterized across a range of material formulations.

With the processing temperature space mapped out, the materials were evaluated using a capillary rheometer to determine the melt viscosities at relevant temperatures. Plasticizers were incorporated to modulate melt viscosity in order to determine the effect of viscosity on bond strength. Bond strength of the materials was evaluated using tensile testing to measure the force required to pull the components apart, and various dosage form configurations that incorporated relevant process and material changes were evaluated for in vivo durability in a beagle model. Through thermal and rheological analyses of the process we were able to reformulate the modular layers and choose the appropriate process parameters to improve bonding without negatively impacting the performance of each component.