Novel 3D Printed Architectures for Oral Long-Acting Drug Delivery Systems Project Summary Long-acting oral (LAO) dosage forms may offer significant benefits for managing chronic medical conditions requiring long-term and intensive medication regimens, particularly those in which observed therapy would be practical and advantageous, such as psychiatric disorders. Poor patient adherence and persistence to therapy are a significant challenge in the schizophrenia patient population, leading to relapse, hospitalizations, and loss of productivity. Extended drug delivery reduces dosing frequency, alleviates pill burden on patients and caregivers, and improves medication adherence. Compared to intramuscular injections, oral dosage forms may improve adoption among patients and clinicians and are cost-effective and more easily administered. Lyndra has developed a LAO delivery system based on a gastric residence technology that can achieve sustained therapeutic drug levels in-vivo for over one week. Lyndra?s LAO therapies have complex geometry, multiple polymeric material components, and intricate assembly and manufacturing requirements involving extrusion, injection molding, and welding. 3D printing is an alternative manufacturing methodology with substantial practical advantages. Novel internal microarchitectures that can only be achieved with 3D printing (3DP) have the potential to overcome challenges with zero-order release kinetics and enable tunable mechanical properties to favor safe gastric residence and exit. The goal of this grant is to develop a novel manufacturing method using fused deposition modeling based 3DP techniques to create novel microarchitectures that enhance the drug delivery and mechanical properties of LAO formulations of risperidone. 3DP provides precise control over the geometry and composition of Lyndra?s solid oral polymeric systems and enables easy modification of dosage form parameters to suit different drug profiles. We believe that this approach will produce high-quality LAO formulations with customizable release profiles and mechanical strength to substantially improve real world performance.
In Aim 1 we will focus on optimizing architectures to achieve near linear in-vitro release rates.
In Aim 2 and 3, we will focus on fabricating architectures with structural elements for improving the mechanical stability of the drug-loaded segments and the linkages connecting adjacent drug-loaded segments in the formulation. Successful proof-of-concept 3DP Phase I studies will lead to a Phase II SBIR that would include preclinical in-vivo pharmacology and safety studies, stability testing, GMP methods of 3DP manufacturing, and IND-enabling toxicology. Novel LAO therapies may offer improved treatment paradigms for patients with schizophrenia and other chronic diseases.
Lyndra has developed an oral ultra long-acting gastric residence technology that enables week-long sustained delivery of drug from a single capsule. These novel formulations require precise drug delivery kinetics and mechanical properties and their complex geometry mandate adoption of novel manufacturing techniques. 3D printing methods offer the potential to improve the manufacturing process and performance of once-weekly long-acting oral therapies such as anti-psychotics via the creation of novel microarchitectures that acheive the precision and flexibility necessary to finely tune drug release and mechanical stability profiles.